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Results for “Enhancer mapping”

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PubMed2026

Transposable element-driven expansion of enhancer RNA repertoires underlies regulatory innovation and polyploid adaptation in cereal crops.

Cereal genomes have undergone repeated polyploidization and transposable element (TE) proliferation, collectively generating complex regulatory landscapes. However, the evolutionary trajectories and functional implications of these landscapes remain largely unexplored. Using chromatin-bound RNA sequencing across seven cereal species, we systematically mapped 45,952 regulatory element transcripts (RETs), including 32,867 distal RETs corresponding to enhancer RNAs (eRNAs). Our analysis revealed that 56% of lineage-specific eRNAs originated from TE expansions, indicating that TEs serve as major reservoirs of species-specific regulatory innovation in cereals. Notably, we identified remarkable conservation in defense-related functions, root-specific expression, and TE-derived origins of eRNAs across both ancient and recent evolutionary layers of Triticeae, suggesting recurrent recruitment of TE-derived, root-associated regulatory elements throughout Triticeae evolution. Furthermore, we found that young eRNA pairs in hexaploid wheat with high sequence similarity, many originating from RLG_famc8.3 and DTC_famc4.3, exhibited pronounced root specificity and coordinated expression, suggesting targeted amplification and refinement of successful ancestral regulatory strategies established after Triticeae divergence. To facilitate community access, we developed Cereal-eRNAdb (http://bioinfo.cemps.ac.cn/Cereal-eRNAdb/), a comprehensive database integrating 69,426 eRNAs with functional annotations across 296 samples. Our findings suggest that TE-mediated innovation of root-specific eRNAs may contribute to Triticeae adaptation and provide a foundational resource for exploiting regulatory variation in cereal crop breeding.

Enhancer RNAs↗

PubMed2025

dbscATAC: a resource of single-cell super-enhancers/enhancers and gene markers derived from scATAC-seq data.

MOTIVATION: scATAC-seq enables high-resolution mapping of cis-regulatory elements. It has been widely applied to uncover cell-type-specific regulatory networks and complement scRNA-seq analysis in numerous studies. However, a large number of datasets generated by scATAC-seq remain underutilized due to limited exploration of super-enhancers/typical enhancers and gene markers. A comprehensive resource enabling cell-type-specific annotation of cis-regulatory elements and their dynamic enhancer-gene linkages remains an urgent unmet need for scATAC-seq. RESULTS: We present dbscATAC, a specialized single-cell database for annotating super-enhancers, gene markers, and enhancer-gene interactions derived from scATAC-seq data. Using improved machine learning algorithms, we identified 213 835 super-enhancers across 520 tissue/cell types from three species, as well as 347 484 gene markers, 13 470 526 enhancers, and 10 402 346 enhancer-gene interactions derived from 1 668 076 single cells spanning 1028 tissue/cell types in 13 species. An easy-to-use online platform with multiple analytic modules and hierarchical query options was developed for searching, browsing and visualizing single-cell super-enhancers, enhancers, and gene markers. dbscATAC provides a comprehensive resource to facilitate the exploration of enhancer landscapes, gene regulation, and cell-type-specific characteristics in single-cell epigenomics. AVAILABILITY AND IMPLEMENTATION: The database with all the super-enhancer/enhancer annotation data is available at http://singlecelldb.com/dbscATAC/index.php. And the source code of dbscATAC for prediction of SEs, enhancers, and gene markers are available at https://github.com/EvansGao/dbscATAC. The source code, tissue/cell type description, and data summary can be downloaded at DOI: 10.6084/m9.figshare.28706414.scATAC-seq, Database, Super-enhancers/enhancers, Gene markers.

Enhancer Elements, Genetic↗

PubMed2025

Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal-like and malignant urothelial cells.

Epigenetic regulators, such as the SWI/SNF complex, with important roles in tissue development and homeostasis, are frequently mutated in cancer. ARID1A, a subunit of the SWI/SNF complex, is mutated in approximately 20% of all bladder tumors; however, the consequences of this remain poorly understood. Finding truncations to be the most common mutation, we generated loss- and gain-of-function models to conduct RNA-Seq, interactome analyses, Omni-ATAC-Seq, and functional studies to characterize ARID1A-affected pathways potentially suitable for the treatment of ARID1A-deficient bladder cancers. We observed decreased cell proliferation and deregulation of stress-regulated pathways, including DNA repair, in ARID1A-deficient cells. Furthermore, ARID1A was linked to alternative splicing and translational regulation on RNA and interactome levels. ARID1A deficiency drastically reduced the accessibility of chromatin, especially around introns and distal enhancers, in a functional enrichment analysis. Less accessible chromatin areas were mapped to pathways such as cell proliferation and DNA damage response. Indeed, the G2/M checkpoint appeared impaired after DNA damage in ARID1A-deficient cells. Together, our data highlight the broad impact of ARID1A loss and the possibility of targeting proliferative and DNA repair pathways for treatment.

Transcription Factors↗

PubMed2027

Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.

Aberrant three-dimensional genome organization is a hallmark of cancer, often driving oncogene activation through mechanisms such as enhancer hijacking. High-throughput chromosome conformation capture (Hi-C) maps these interactions on a genome-wide scale. Unlike earlier dilution-based methods, in situ Hi-C performs proximity ligation within intact nuclei, minimizing random ligation noise and enabling fine-scale structure detection. This chapter describes an optimized in situ Hi-C protocol tailored for cancer cell lines using MboI digestion and biotin-mediated pull-down to generate high-complexity libraries. We further outline a computational workflow that extends beyond standard topological mapping of compartments and topologically associating domains to identify cancer-specific aberrations. Specifically, we focus on detecting chromosomal rearrangements (structural variants) and characterizing the distinct circular topology of extrachromosomal DNA. This integrated experimental and analytical framework provides the necessary tools to dissect the spatial dysregulation underlying tumor evolution.

Humans↗

PubMed2014

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Adolescent↗

PubMed2026

Diffusion MRI radiomics in meningiomas: imaging correlates of tumor grade and intraoperative consistency.

OBJECTIVE: Despite advancements in imaging studies, the preoperative prediction of the biological behavior and intraoperative consistency of intracranial meningiomas remains limited. This study evaluated the association of volumetric diffusion-based and texture-derived radiomic features extracted from routine MRI with histopathological aggressiveness and intraoperative tumor consistency. METHODS: Ninety-seven intracranial meningiomas resected at two tertiary centers were retrospectively analyzed. Volumetric segmentation was performed on contrast-enhanced T1-weighted MRI and coregistered to apparent diffusion coefficient (ADC) maps. Data on first-order diffusion metrics and selected texture features were collected. The associations between World Health Organization (WHO) grade and Ki-67 index were assessed using nonparametric tests and Spearman correlation analysis. Independent factors associated with intraoperative tumor consistency (Zada grades 1-5) were evaluated via multivariate ordinal logistic regression analysis that adjusted for tumor volume, skull base location, calcification status, and WHO grade. Secondary receiver operating characteristic (ROC) curve analyses were performed to differentiate solid (Zada grades 4-5) from soft (Zada grades 1-2) tumors. ROC analyses were performed within the study cohort and were intended as exploratory assessments of discriminative performance. RESULTS: The mean ADC (ADCmean) and the 10th percentile of the ADC decreased significantly with increasing WHO grade (p < 0.001). ADCmean had a moderate inverse correlation with the Ki-67 index (r = -0.42, p < 0.001) and intraoperative tumor consistency (r = -0.45, p < 0.001). In the multivariate analysis, the ADCmean remained independently associated with increasing tumor firmness. Each 0.1 × 10-3 mm2/sec increase corresponded to a 38% reduction in the odds of belonging to a higher consistency category (OR 0.62, 95% CI 0.51-0.74, p < 0.001). The ROC analysis showed good discrimination for solid tumors (area under the curve 0.847, 95% CI 0.742-0.953) and soft tumors (area under the curve 0.824, 95% CI 0.714-0.935). Texture features had weaker associations with intraoperative tumor consistency. CONCLUSIONS: Volumetric diffusion-derived metrics, particularly ADCmean, are associated with both histopathological aggressiveness and intraoperative tumor firmness in meningiomas. Diffusion imaging may reflect a graded microstructural continuum rather than a purely dichotomous property, providing complementary preoperative insights into surgical complexity.

Humans↗

PubMed2026

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 ± 0.0994, with a Log-rank testp-value of 1.6553×10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 ± 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 ± 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 ± 0.1211) and discrete-time survival models such as DeepHit (0.7655 ± 0.1041) and Nnet-surv (0.7694 ± 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 ± 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 ± 0.0818) and Multimodal Co-Attention Transformer (0.8102 ± 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell↗

PubMed2025

The Fire Ant Social Chromosome Exerts a Major Influence on Genome Regulation.

Supergenes underlying complex trait polymorphisms ensure that sets of coadapted alleles remain genetically linked. Despite their prevalence in nature, the mechanisms of supergene effects on genome regulation are poorly understood. In the fire ant Solenopsis invicta, a supergene containing over 500 individual genes influences trait variation in multiple castes to collectively underpin a colony level social polymorphism. Here, we present results of an integrative investigation of supergene effects on gene regulation. We present analyses of ATAC-seq data to investigate variation in chromatin accessibility by supergene genotype and STARR-seq data to characterize enhancer activity by supergene haplotype. Integration with gene co-expression analyses, newly mapped intact transposable elements (TEs), and previously identified copy number variants (CNVs) collectively reveals widespread effects of the supergene on chromatin structure, gene transcription, and regulatory element activity, with a genome-wide bias for open chromatin and increased expression in the presence of the derived supergene haplotype, particularly in regions that harbor intact TEs. Integrated consideration of CNVs and regulatory element divergence suggests each evolved in concert to shape the expression of supergene encoded factors, including several transcription factors that may directly contribute to the trans-regulatory footprint of a heteromorphic social chromosome. Overall, we show how genome structure in the form of a supergene has wide-reaching effects on gene regulation and gene expression.

Animals↗

PubMed1976

Ouabain-binding and phosphorylation of (Na+ + K+) ATPase treated with N-ethylmaleimide or oligomycin.

Ouabain-binding and phosphorylation of (Na+ mk+)-ATPase (EC 3.6.1.3) of the plasma membranes from kidney were investigated after treatment with N-ethylmaleimide or oligomycin. Either of these inhibitors brought about the following changes: the phosphoenzyme, formed in the presence of Na+, Mg2+ and ATP became essentially insensitive to splitting by K+ but was split by ADP. One mole of this ADP-sensitive phosphoenzyme bound one mole of ouabain but the enzyme-ouabain complex was less stable than in the native enzyme primarily because the rate of its dissociation increased. Ouabain was bound to the ADP-sensitive phosphoenzyme in the presence of Mg2+ alone and addition of inorganic phosphate enhanced both the rate of formation and the steady-state level of the enzyme-ouabain complex. The inhibitors did not affect the properties of this second type of complex. Both in the native enzyme and in the enzyme treated with the two inhibitors inorganic phosphate enhanced ouabain binding by phosphorylating the active center of the enzyme as shown (a) by mapping the labeled peptides from the enzyme after peptic digestion, (b) by inhibition of this phosphorylation with Na+ and (c) by the 1:1 stoichiometric relation between this phosphorylation and the amount of bound ouabain. Unlike the phosphoenzyme, the binding of ouabain remained sensitive to K+ in the enzyme treated with the inhibitors. K+ slowed ouabain-binding either in the presence of Na+, Mg2+ and ATP or of Mg2+ and inorganic phosphate. A higher concentration of K+ was needed to slow ouabain-binding either in the presence of Na+, Mg2+ and ATP or of Mg2+ and inorganic phosphate. A higher concentration of K+ was needed to slow ouabain-binding than to stimulate dephosphorylation. This finding is interpreted as being an indication of separate sites for K+ on the enzyme: a site(s) with high K+-affinity which stimulates dephosphorylation, another site(s) with moderate K+-affinity which inhibits ouabain-binding. Inhibitors may enhance formation of the ADP-sensitive phosphoenzyme by blocking interaction between K+ and the site(s) with high affinity.

Adenosine Triphosphatases↗

PubMed1979

Interaction of purple membrane with solvents. II. Mode of interaction.

Using the solubility parameter mapping technique (Eisenbach, M., Caplan, S.R. and Tanny, G (1979) Biochim. Biophys. Acta 554, 269-280) we studied spectroscopically the mode of interaction between the purple membrane of Halobacterium halobium and pure organic solvents or solvent mixtures. Although the interacting solvents formed a well-defined closed region in the interaction maps, mapping the modes of interaction did not reveal a closed region for each spectrally classifiable type. A suggested interpretation for this is that interaction with the purple membrane chromophore requires that a solvent (or solvent mixture) possess apolar groups in order to obtain access to the chromophore, together with a polar character and hydrogen-bonding capacity. The mode of interaction, however, is dependent on the specificity of the reactive group of the solvent for retinal, and this has nothing to do with membrane properties. We also examined the influence of the duration of the interaction and of illumination. Some solvents appeared to react more sluggishly than others, but no generalization in terms of the solubility parameter mapping was found, probably because the map describes thermodynamic rather than kinetic phenomena. The only effect of illumination was to enhance the reaction of some of these solvents. It did not change the solubility parameters of purple membrane.

Bacteriorhodopsins↗

PubMed1976

Lambda cin-1, a new mutation which enhances lysogenization by bacteriophage lambda, and the genetic structure of the lambda cy region.

Seven lambda cy mutants have been mapped within a small region located approximately halfway between the rightward boundary of the imm434 region and the lambda cII gene. The seven mutants lie at four sites separated by a total distance of about 12 nucleotide pairs, as estimated from recombination frequencies. Six of the seven mutants lie on the right side of the cy fine structure map, spanning a total distance of about 3-5 nucleotide pairs. Lying approximately 11-21 nucleotide pairs to the left of the leftmost cy mutant is a newly described mutation called cin-1, for c independent. The cin-1 mutation allows some lysogenization when coupled with any cy, cII or cIII mutant, but not when coupled with a defective cI gene. The cin-1 mutation, like cy mutants, has a cis-dominant action upon the cI gene in mixed infections. The observation that gammaimm434 cin-1-cy2001 lysogenizes efficiently, but not gammaimm434 cin-1 cy2001 cII68 nor any other gammaimm434 cin-1 cy derivative, is interpreted to mean that all of the cy mutants on the right side of the cy fine structure map inactivate a binding site for cII/cIII function, but that cy2001, the single mutant on the left side of the cy fine structure map, does not inactivate that binding site.

Chromosome Mapping↗

PubMed2026

Epigenetic alterations in rheumatoid arthritis: multilayer mechanisms and translational opportunities.

Rheumatoid arthritis (RA) is a chronic inflammatory disease driven by immune dysregulation, in which genetic susceptibility and environmental exposures promote persistent synovitis, progressive joint damage, and systemic comorbidities. Recent epigenomic studies show several recurring abnormalities. Many RA susceptibility variants lie outside protein-coding sequence and map to immune-cell and synovial fibroblast regulatory elements, linking inherited risk to enhancer activity, methylation quantitative trait effects, and distal gene control. Blood-based epigenome-wide association studies identify disease-associated DNA methylation signatures, but these signals require careful control for leukocyte composition, smoking, treatment exposure, and disease stage. RA fibroblast-like synoviocytes also display stable methylome remodeling, including relative hypomethylation at loci involved in inflammation, migration, matrix degradation, and apoptosis resistance, while TET3-associated 5-hydroxymethylcytosine has emerged as a functional contributor to chemokine production and invasive stromal behavior. Histone modifications, chromatin accessibility, and 3D genome organization define pathogenic regulatory states and connect non-coding risk loci to effector genes in immune and stromal compartments. Finally, miRNAs, lncRNAs, circRNAs, snoRNAs, extracellular RNAs, and m6A-related pathways add post-transcriptional and chromatin-linked layers with potential biomarker value. We synthesize these findings and discuss translational opportunities for diagnosis, stratification, flare monitoring, and therapeutic targeting, while emphasizing incomplete replication, uneven evidence across epigenetic layers, biospecimen variability, and the need for causal, longitudinal, cell-type-resolved validation.

Humans↗

PubMed2026

Clone and characterization of a cytochrome P450 gene for drought tolerance in rice.

BACKGROUND: Drought is a major abiotic stress limiting rice production worldwide. Identifying genes that enhance drought tolerance is essential for breeding resilient varieties. RESULTS: In this study, we report the map-based cloning and functional characterization of DT1, a novel cytochrome P450 gene conferring drought tolerance in rice. Using near isogenic lines (NILs) derived from a cross between Xiang743 and Katy, we delimited DT1 into a 115 kb interval on chromosome 3, where contains 18 open read frames (ORFs). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified Os03g55250 as the candidate gene. Clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR/Cas9) knockout mutants of Os03g55250 exhibited increased drought sensitivity, while overexpression lines showed enhanced drought tolerance, confirming that Os03g55250 was the target gene and positively regulates drought resistance. DT1 was mainly expressed in stems, leaves, and leaf sheaths, and the DT1 protein localized in the endoplasmic reticulum. Haplotype analysis identified Hap1 as a favorable allele in japonica rice. CONCLUSIONS: Our findings provide a promising genetic resource for breeding drought-resistant rice varieties and offers new insights into the role of P450 genes in abiotic stress adaptation.

Oryza↗

PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.

ancient DNA↗

PubMed2025

Analysis of Blood Microbiome From People Living With HIV and Donors by 16S rRNA Metagenomic Sequencing.

Utilize 16S rRNA sequencing technology to characterize bacterial species susceptible to people living with HIV (PLWH) across different stages. This mapping aims to establish a foundational framework for preventing secondary HIV infections, prolonging patient survival, enhancing quality of life, and advancing the diagnosis, treatment, and research of bacterial co-infections. In this study, we classified the participants into three groups: The blood of donors living with HIV (DI group), AIDS patients who have received ART treatment (PI group), and healthy blood donors as the control group (DH group). Each group was divided into three parallel subgroups, with 30 samples pooled from each parallel group for plasma extraction. As initial processing steps, the nine parallel subgroups were subjected to nucleic acid extraction and PCR amplification targeting the 16SV34 region. The resulting amplified products were subsequently forwarded to a sequencing company. It can be seen from the Venn diagram that the DI groups showed significantly higher bacterial diversity than the PI group and the DH group. The PI group had lower bacterial relative abundance and diversity compared to the DI group, with a community structure more similar to the control group. The DI group is particularly susceptible to several significant pathogens, including Ralstonia, Pseudomonas, Acinetobacter, Methyloversatilis, and Vibrio. The study revealed a greater quantity and diversity of bacteria in the DI blood compared to the PI and DH groups. This observation may be attributed to PI group patients in this study being hospitalized and receiving treatment.

Humans↗

PubMed1976

Site c27 in phage P22 and control of the pathway to lysogeny.

Phage P22 mutation c27 defines a site required for establishment , but not maintenance of repressor synthesis. This study confirms that P22 c27 is able to synthesize repressor if active repressor is present. An interaction involving gene products of c1 and c3 and the site c27 retards expression of the lytic genes of P22. Mutations in gene c1 eliminate the retardation of lytic gene expression, but c27 does not alleviate the retardation. These results are used to construct a model that postulates that binding of c1 and c3 products to DNA at or near c27 is sufficient to cause retardation of lytic gene expression. The functioning of c27 is contrasted to that of the analogous cy mutants of lambda. The effect of the c27 mutation upon alleviation of "cl repression" was studied in a partial revertant of Salmonella typhimurium Pox-1 in which c1 repression is exaggerated. The higher frequency of lysogenization seen in the mutant host is related to enhanced cl repression.

Base Sequence↗

PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

UNLABELLED: Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in IFN-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of a homologous risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent genetic IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits. HIGHLIGHTS: Genetic analysis using modern and evolutionary datasets identifies a persistent and highly prevalent lupus-associated coding haplotype in IRF7 at 11p15 The IRF7 lupus risk haplotype increases IFN-α production by monocytes and airway epithelial cells The IRF7 lupus risk haplotype increases IRF7 DNA binding strength and alters DNA sequence specificity A homologous lupus risk variant in mouse Irf7 enhances control of vesicular stomatitis virus and exacerbates autoantibody production.

Journal Article↗

PubMed2003

MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300.

CBP/p300 recruitment to enhancer-bound complexes is a key determinant in promoter activation by many transcription factors. We present a novel mechanism of activating such complexes and show that pre-assembled Elk-1-p300 complexes become activated following Elk-1 phosphorylation by changes in Elk-1-p300 interactions rather than recruitment. It is known that Elk-1 binds to promoter in the absence of stimuli. However, it is unclear how activation of Elk-1 by mitogen-acivated protein kinase (MAPK)-mediated phosphorylation leads to targeted gene transactivation. We show that Elk-1 can interact with p300 in vitro and in vivo in the absence of a stimulus through the Elk-1 C-terminus and the p300 N-terminus. Phosphorylation on Ser383 and Ser389 of Elk-1 by MAPK enhances this basal binding but, most importantly, Elk-1 exhibits new interactions with p300. These interaction changes render a strong histone acetyltransferase activity in the Elk-1-associated complex that could play a critical role in chromatin remodeling and gene activation. The pre-assembly mechanism may greatly accelerate transcription activation, which is important in regulation of expression of immediate-early response genes, in particular those involved in stress responses.

Acetyltransferases↗