Biomedical subjects

Ke Zhang

Publications and source records attributed to Ke Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide.

Environmental hypoxia exerts detrimental effects on the reproductive capabilities of both humans and animals. A fetal hypoxia model was established in which fetal mice were kept in a high-plateau hypoxic setting from embryonic day (E) 0 to 16.5. In our previous research, we found that fetal hypoxia exposure perturbs the methylation of imprinted genes in adult sperm and causes intergenerational placental impairments in male offspring. However, the specific impacts of fetal hypoxia on the female reproductive system, particularly regarding oocyte maturation, remain poorly understood. First, we found that fetal hypoxia mice exhibited a significant reduction in the average number of pups per litter. We conducted a comprehensive analysis of the transcriptome in oocytes from the hypoxic group and investigated the metabolic alterations within the follicular microenvironment. Fetal hypoxic stress contributed to cleavage and blastocyst rate reduction and induced early apoptosis and DNA damage triggered by mitochondrial dysfunction, oxidative stress aggravation and Sirt3/Sod2 downregulation. Additionally, administration of nicotinamide mononucleotide (NMN) has been shown to prevent oocytes from mitochondrial dysfunction and developmental impairment by increasing the expression of Sirt3/Sod2 and autophagy. The number of pups per litter in fetal hypoxia mice was reduced by 57.7% compared to the control group, while NMN intervention could restore it to 73.1% of the control group. These results indicate that fetal hypoxia exposure exerts multiple potential damages to adult female reproduction, while highlighting the clinical potential of NMN supplementation as a targeted intervention to alleviate such hypoxia-associated female reproductive impairment.

Animals↗

PubMed2026

Causal relationship between asthma and hernia risk: A Mendelian randomization study.

Epidemiological associations between asthma and various hernia subtypes have been reported, but the causality and direction remain unclear. This study employs a two‑sample Mendelian randomization (MR) approach to systematically assess the causal associations between asthma and 6 hernia subtypes. Using publicly available summary data of genome-wide association studies, asthma was selected as the exposure, and diaphragmatic hernia, umbilical hernia, femoral hernia, hiatus hernia, inguinal hernia, and ventral hernia were selected as outcomes. Instrumental variables were strictly screened (F-statistic > 10). The inverse‑variance weighted method was used as the primary analytical approach, supplemented with MR Egger and weighted median methods. Sensitivity analyses included heterogeneity tests, horizontal pleiotropy tests, Steiger directionality tests, leave‑one‑out analyses, and Radial MR. Reverse MR was performed for validation. Forward MR analyses revealed a significant positive causal effect of asthma on diaphragmatic hernia (odds ratio [OR] = 1.19, 95% confidence interval [CI]: 1.08-1.31, P < .001) and a suggestive association with umbilical hernia (OR = 1.19, 95% CI: 1.05-1.34, P = .007). The umbilical hernia association was significant only by the inverse‑variance weighted method; weighted median (P = .102) and MR-Egger (P = .210) estimates were not statistically significant, and the estimate attenuated after outlier removal (confirmatory OR = 1.13, 95% CI: 1.01-1.26, P = .028). Sensitivity analyses showed no significant heterogeneity or pleiotropy. Reverse MR did not identify significant causal effects of hernias on asthma, although power limitations for certain hernia subtypes should be considered. No significant associations were observed between asthma and the other hernia subtypes, although the null findings for femoral and ventral hernias should be interpreted with caution due to limited statistical power. This study provides genetic evidence supporting asthma as a causal risk factor for diaphragmatic hernia, with a suggestive association for umbilical hernia. The diaphragmatic hernia finding was robust across multiple sensitivity analyses, whereas the umbilical hernia association was less consistent and requires further confirmation. These findings contribute to a deeper understanding of the mechanistic links between asthma and specific hernia subtypes.

Mendelian Randomization Analysis↗

PubMed2026

Phenacetin inhibited but acetaminophen stabilized partial nitrification/anammox system: Studies on microbial metabolism and resistance genes in biofilm and plastisphere.

Partial nitrification (PN) inhibitors, such as phenacetin (PNCT) and acetaminophen (APAP), ensure a stable nitrite supply for anaerobic ammonium oxidation (anammox). But the unknown impact of inhibitors on anammox limit the application of inhibitors. In addition to the biofilm carriers used in biological nitrogen removal systems, microplastics (MPs) (a type of emerging contaminants) are the common substrate for microbial colonization, even enriched resistance genes (RGs). This research compared the effects of 0.5, 1 and 5 mg/L PNCT or APAP on partial nitrification-anammox (PN/A) biofilm and plastisphere. 1 mg/L PNCT inhibited the nitrogen removal functional bacteria (Nitrosomonas, Candidatus Kuenenia, Candidatus Brocadia and Nitrospira), resulting in the sharp deteriorated performance of PN/A system. 5 mg/L PNCT inhibited multiple metabolism pathways, resulting in the absence of electrons and energy supply of microorganisms. 0.5-1 mg/L APAP maintained the stable operation of PN/A system. Nitrospira abundances declined from 2.8% to 1.1% after 0.5 mg/L APAP exposure. But 5 mg/L APAP inhibited the abundance of amoA and the production of extracellular polymeric substances, which caused the slight fluctuation of PN/A performance. PN inhibitors did not cause the sharp increase of most RGs in biofilm and water. However, MPs exhibited the huge capacity of enriching RGs, which should be removed. This study proposed that 0.5 mg/L of APAP was suitable for the PN/A system to control dosage for practical application.

Biofilms↗

PubMed2026

Comparative transcriptome analysis of Qinchuan and Wagyu cattle reveals lnc11599 as a negative regulator of intramuscular fat deposition.

BACKGROUND: Intramuscular fat (IMF) content is a critical factor determining beef quality, influenced by various factors including breed and age. However, the regulatory role of long non-coding RNAs (lncRNAs) in IMF deposition remains unclear. METHODS: This study investigated IMF deposition in the longissimus dorsi muscle of one- and two-year-old Qinchuan and Wagyu cattle through histological examination and fat content measurement. Based on transcriptome sequencing data of intramuscular fat tissue, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify lncRNAs associated with IMF deposition. The effects of a key candidate lncRNA on the adipogenic differentiation of cattle intramuscular preadipocytes were further examined. RESULTS: Results showed that Wagyu cattle exhibited stronger IMF deposition capacity than Qinchuan cattle across all age groups, with IMF content increasing with age in both breeds. We identified 7,910 lncRNAs from intramuscular fat tissue transcriptome data, including 6,455 novel lncRNAs. Through integrated differential expression analysis and WGCNA, 88 lncRNAs closely associated with IMF deposition were screened from two-year-old Qinchuan and Wagyu cattle. Notably, lnc11599 was significantly upregulated in Qinchuan cattle intramuscular fat tissue, but its expression decreased during intramuscular preadipocyte differentiation. Functional experiments demonstrated that lnc11599 knockdown enhanced adipogenic differentiation capacity, manifested as a highly significant increase in lipid accumulation, upregulation of key adipogenic genes at the mRNA level, together with increases in total fatty acid content and unsaturated fatty acid proportion. CONCLUSIONS: This study established the lncRNA expression profiles in intramuscular fat tissue of Qinchuan and Wagyu cattle across different developmental stages, and demonstrated that lnc11599 acts as a negative regulator of intramuscular fat deposition. These findings provide new directions for elucidating the mechanisms of cattle IMF deposition and offer potential targets for genetic improvement of beef quality.

Animals↗

PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS ≪ 1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗

PubMed2026

CRISPR-mediated intronic knock-in of pre-amiRNA enables targeted gene silencing.

This study introduces an intronic artificial microRNA (IamiRNA) strategy that combines CRISPR-Cas9-mediated knock-in with endogenous miRNA processing for targeted gene silencing in plants. By inserting amiRNA precursors into introns of endogenous genes, this approach enables effective, tissue-specific gene silencing without persistent transgene expression, offering a promising tool for functional genomics and crop improvement.

Introns↗

PubMed2026

A 7-mm Covered TIPS Reduces Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters < 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n = 92) or 8-mm (n = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, p = 0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans↗

PubMed2006

DNA damage checkpoints are involved in postreplication repair.

Saccharomyces cerevisiae MMS2 encodes a ubiquitin-conjugating enzyme variant, belongs to the error-free branch of the RAD6 postreplication repair (PRR) pathway, and is parallel to the REV3-mediated mutagenesis branch. A mutation in genes of either the MMS2 or the REV3 branch does not result in extreme sensitivity to DNA-damaging agents; however, deletion of both subpathways of PRR results in a synergistic phenotype. Nevertheless, the double mutant is not as sensitive to DNA-damaging agents as a rad6 or rad18 mutant defective in the entire PRR pathway, suggesting the presence of an additional subpathway within PRR. A synthetic lethal screen was employed in the presence of a sublethal dose of a DNA-damaging agent to identify novel genes involved in PRR, which resulted in the isolation of RAD9 as a candidate PRR gene. Epistatic analysis showed that rad9 is synergistic to both mms2 and rev3 with respect to killing by methyl methanesulfonate (MMS), and the triple mutant is nearly as sensitive as the rad18 single mutant. In addition, rad9 rad18 is no more sensitive to MMS than the rad18 single mutant, suggesting that rad9 plays a role within the PRR pathway. Moreover, deletion of RAD9 reduces damage-induced mutagenesis and the mms2 spontaneous and induced mutagenesis is partially dependent on the RAD9 gene. We further demonstrated that the observed synergistic interactions apply to any two members between different branches of PRR and G1/S and G2/M checkpoint genes. These results suggest that a damage checkpoint is essential for tolerance mediated by both the error-free and error-prone branches of PRR.

Cell Cycle↗

PubMed2006

Resonant-pattern formation induced by additive noise in periodically forced reaction-diffusion systems.

We report frequency-locked resonant patterns induced by additive noise in periodically forced reaction-diffusion Brusselator model. In the regime of 2:1 frequency-locking and homogeneous oscillation, the introduction of additive noise, which is colored in time and white in space, generates and sustains resonant patterns of hexagons, stripes, and labyrinths which oscillate at half of the forcing frequency. Both the noise strength and the correlation time control the pattern formation. The system transits from homogeneous to hexagons, stripes, and to labyrinths successively as the noise strength is adjusted. Good frequency-locked patterns are only sustained by the colored noise and a finite time correlation is necessary. At the limit of white noise with zero temporal correlation, irregular patterns which are only nearly resonant come out as the noise strength is adjusted. The phenomenon induced by colored noise in the forced reaction-diffusion system is demonstrated to correspond to noise-induced Turing instability in the corresponding forced complex Ginzburg-Landau equation.

Journal Article↗

PubMed2006

Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation.

Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igmu/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Imu-BCL6E2 and BCL6E1-Cmu1 transcripts that reflect reciprocal Igmu/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igmu/BCL6 CT and were not generated from trans-splicing. Both Imu-BCL6E2 and BCL6E1-Cmu1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Imu-BCL6 transcripts. The appearance of Igmu/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center-stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.

B-Lymphocytes↗

PubMed2006

A chimeric human-cat Fcgamma-Fel d1 fusion protein inhibits systemic, pulmonary, and cutaneous allergic reactivity to intratracheal challenge in mice sensitized to Fel d1, the major cat allergen.

Co-aggregation of FcepsilonRI with FcgammaRIIb can block FcepsilonRI-mediated reactivity and Fc gamma:allergen chimeric proteins, by co-crosslinking FcgammaRIIb to allergen-specific IgE bound to the FcepsilonRI can block allergen-specific reactivity. We evaluated whether a human cat chimeric fusion protein (GFD) composed of part of the human Ig G1 Fc fused to the major cat allergen (Fel d1) would function as allergen immunotherapy while not inducing acute allergic reactivity in mice sensitized to Fel d1. Injection of GFD 6 h prior to Fel d1 challenge acutely blocked systemic and skin reactivity to Fel d1 challenge while mice given subcutaneous immunotherapy with GFD at days 37, 38, and 39 showed inhibition of systemic, lung, and cutaneous reactivity to Fel d1 2 weeks later. GFD immunotherapy did not induce systemic reactivity. Overall, the Fcgamma-Fel d1 chimeric fusion protein blocked Fel d1-induced IgE-mediated reactivity but did not induce in vivo mediator release on its own; suggesting that this approach using allergen combined with Fc gamma1 so as to achieve inhibitory signaling may provide an enhanced form of allergen immunotherapy.

Animals↗

PubMed2006

Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors.

c-Met is a well-characterized receptor tyrosine kinase for hepatocyte growth factor (HGF). Compelling evidence from studies in human tumors and both cellular and animal tumor models indicates that signaling through the HGF/c-Met pathway mediates a plethora of normal cellular activities, including proliferation, survival, migration, and invasion, that are at the root of cancer cell dysregulation, tumorigenesis, and tumor metastasis. Inhibiting HGF-mediated signaling may provide a novel therapeutic approach for treating patients with a broad spectrum of human tumors. Toward this goal, we generated and characterized five different fully human monoclonal antibodies that bound to and neutralized human HGF. Antibodies with subnanomolar affinities for HGF blocked binding of human HGF to c-Met and inhibited HGF-mediated c-Met phosphorylation, cell proliferation, survival, and invasion. Using a series of human-mouse chimeric HGF proteins, we showed that the neutralizing antibodies bind to a unique epitope in the beta-chain of human HGF. Importantly, these antibodies inhibited HGF-dependent autocrine-driven tumor growth and caused significant regression of established U-87 MG tumor xenografts. Treatment with anti-HGF antibody rapidly inhibited tumor cell proliferation and significantly increased the proportion of apoptotic U-87 MG tumor cells in vivo. These results suggest that an antibody to an epitope in the beta-chain of HGF has potential as a novel therapeutic agent for treating patients with HGF-dependent tumors.

Animals↗

PubMed2005

Histone modifying enzymes and cancer: going beyond histones.

Mutations in the molecular pathways that regulate cell proliferation, differentiation, and cell death all contribute to cancer formation. Enzymes that covalently modify histones affect these pathways by controlling the dynamic remodeling of chromatin structure. This article reviews several connections between histone modifying enzymes and cancer that are likely mediated via both histone and non-histone substrates. We propose that multiple protein modifications, including phosphorylation, methylation, and acetylation, cross regulate one another to coordinate intermolecular signaling, and that miscues in this regulation can lead to oncogenesis.

Animals↗

PubMed2005

[A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulfate in the treatment of knee osteoarthritis].

OBJECTIVE: To evaluate the efficacy and safety of glucosamine hydrochloride (GH) in the treatment of patients with knee osteoarthritis (OA) comparing with glucosamine sulfate (GS). METHODS: A multi-central, randomized, parallel-controlled clinical trial of GH vs GS was performed. 142 patients suffering from knee OA were randomized into 2 groups, treated with GH and GS for 480 mg and 500 mg one time respectively. Patients received medicine 3 times daily with total 1440 mg per day for GH group and 1500 mg for GS group, orally for 4 weeks and were assessed for drug efficacy and safety for 2 more weeks. Knee pain at rest, at movement and at pressure, knee swelling, morning stiffness and walking ability were recorded at 1, 2, 3, 4 and 6 week according to Lequesne's criteria. Other features such as therapeutic efficacy, adverse events and laboratory parameters were also recorded. RESULTS: A considerable improvement in OA symptoms and a reduce of total Lequesne's score were observed in both groups after the 4-week treatment. The Lequesne's score decreased to 3.4 +/- 1.9 (P < 0.05) and 3.4 +/- 1.8 (P < 0.05) after 4-week treatment comparing to 0-week in the GH (9.4 +/- 1.8) group and GS (9.5 +/- 1.4) group respectively. There was no significant difference between 2 groups in decreasing the Lequesne's score (P > 0.05). The symptomatic improvement rates in patients were 91.4% and 90.0% at 4-week treatment in the GH and GS group respectively (P > 0.05). There was a remnant therapeutic effect in both groups at 2 weeks after discontinuation of the treatment. And 4.2% (3/71) of patients on GH reported adverse events, vs 7.0% (5/71) adverse events with GS group (P > 0.05), mainly mild stomach discomfort and constipation. CONCLUSION: There were no significant differences in efficacy and safety between GH and GS groups in the treatment of knee OA. Glucosamine hydrochloride is as effective and safe as glucosamine sulfate.

Administration, Oral↗

PubMed2005

The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation.

A balance in the activities of the Ipl Aurora kinase and the Glc7 phosphatase is essential for normal chromosome segregation in yeast. We report here that this balance is modulated by the Set1 methyltransferase. Deletion of SET1 suppresses chromosome loss in ipl1-2 cells. Conversely, combination of SET1 and GLC7 mutations is lethal. Strikingly, these effects are independent of previously defined functions for Set1 in transcription initiation and histone H3 methylation. We find that Set1 is required for methylation of conserved lysines in a kinetochore protein, Dam1. Biochemical and genetic experiments indicate that Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines. Our studies demonstrate that Set1 has important, unexpected functions in mitosis. Moreover, our findings suggest that antagonism between lysine methylation and serine phosphorylation is a fundamental mechanism for controlling protein function.

Amino Acid Sequence↗

PubMed2005

[Effects of prolonged selenium and iodine deficiency on monamine neurotransmitters in the different brain area in developing rats].

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Animals↗

PubMed2005

A chimeric human-cat fusion protein blocks cat-induced allergy.

Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-Fel d1 protein induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release from cat-allergic donors' basophils and sensitized human cord blood-derived mast cells. Such inhibition was associated with altered Syk and ERK signaling. The Fcgamma-Fel d1 protein also blocked in vivo reactivity in FcepsilonRIalpha transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcgamma-Fel d1 protein alone did not induce mediator release. Chimeric human Fcgamma-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.

Animals↗

PubMed2005

Agrobacterium T-DNA integration in Arabidopsis is correlated with DNA sequence compositions that occur frequently in gene promoter regions.

Mobile insertion elements such as transposons and T-DNA generate useful genetic variation and are important tools for functional genomics studies in plants and animals. The spectrum of mutations obtained in different systems can be highly influenced by target site preferences inherent in the mechanism of DNA integration. We investigated the target site preferences of Agrobacterium T-DNA insertions in the chromosomes of the model plant Arabidopsis thaliana. The relative frequencies of insertions in genic and intergenic regions of the genome were calculated and DNA composition features associated with the insertion site flanking sequences were identified. Insertion frequencies across the genome indicate that T-strand integration is suppressed near centromeres and rDNA loci, progressively increases towards telomeres, and is highly correlated with gene density. At the gene level, T-DNA integration events show a statistically significant preference for insertion in the 5' and 3' flanking regions of protein coding sequences as well as the promoter region of RNA polymerase I transcribed rRNA gene repeats. The increased insertion frequencies in 5' upstream regions compared to coding sequences are positively correlated with gene expression activity and DNA sequence composition. Analysis of the relationship between DNA sequence composition and gene activity further demonstrates that DNA sequences with high CG-skew ratios are consistently correlated with T-DNA insertion site preference and high gene expression. The results demonstrate genomic and gene-specific preferences for T-strand integration and suggest that DNA sequences with a pronounced transition in CG- and AT-skew ratios are preferred targets for T-DNA integration.

Arabidopsis↗