Biomedical subjects

Xiaoman Li

Publications and source records attributed to Xiaoman Li.

8 recordsLinked to original sources

PubMed2024

The ARK2N-CK2 complex initiates transcription-coupled repair through enhancing the interaction of CSB with lesion-stalled RNAPII.

Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/- mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER.

DNA Repair Enzymes↗

PubMed2006

A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.

MOTIVATION: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods. AVAILABILITY: The software is available on request from the authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗

PubMed2005

Reliable prediction of transcription factor binding sites by phylogenetic verification.

We present a statistical methodology that largely improves the accuracy in computational predictions of transcription factor (TF) binding sites in eukaryote genomes. This method models the cross-species conservation of binding sites without relying on accurate sequence alignment. It can be coupled with any motif-finding algorithm that searches for overrepresented sequence motifs in individual species and can increase the accuracy of the coupled motif-finding algorithm. Because this method is capable of accurately detecting TF binding sites, it also enhances our ability to predict the cis-regulatory modules. We applied this method on the published chromatin immunoprecipitation (ChIP)-chip data in Saccharomyces cerevisiae and found that its sensitivity and specificity are 9% and 14% higher than those of two recent methods. We also recovered almost all of the previously verified TF binding sites and made predictions on the cis-regulatory elements that govern the tight regulation of ribosomal protein genes in 13 eukaryote species (2 plants, 4 yeasts, 2 worms, 2 insects, and 3 mammals). These results give insights to the transcriptional regulation in eukaryotic organisms.

Base Sequence↗

PubMed2005

Sampling motifs on phylogenetic trees.

We present a method to find motifs by simultaneously using the overrepresentation property and the evolutionary conservation property of motifs. This method is applicable to divergent species where alignment is unreliable, which overcomes a major limitation of the current methods. The method has been applied to search regulatory motifs in four yeast species based on ChIP-chip data in Saccharomyces cerevisiae and obtained 20% higher accuracy than the best current methods. We also discovered cis-regulatory elements that govern the tight regulation of ribosomal protein genes in two distantly related insects by using this method. These results demonstrate that our method will be useful for the extraction of regulatory signals in multiple genomes.

Base Sequence↗

PubMed2005

Maternal immunization with both hemagglutinin- and neuraminidase-expressing DNAs provides an enhanced protection against a lethal influenza virus challenge in infant and adult mice.

Maternal immunization is the major form of protection against many infectious diseases in early life. In this report, transmission of vaccine-specific maternal antibodies and protection of offspring against a lethal influenza virus challenge were studied. Adult female BALB/c mice were immunized intramuscularly with plasmid DNAs encoding influenza virus hemagglutinin (HA), neuraminidase (NA), or mixture of the two plasmids. The levels of specific antibodies in sera of offspring at different ages and the survival rates following the lethal viral challenge were valued. The results showed effective transmission of maternal antibodies and long-lasting protection in offspring. Along with the growth of offspring, the antibody titers in vivo decreased and the ability against virus infection decreased accordingly. The HA-specific maternal antibodies protected the offspring from a lethal influenza infection up to 2 weeks old, and the NA-specific maternal antibodies protected offspring up to 4 weeks old. Furthermore, antibodies transferred by the mother immunized with the mixture of HA and NA DNAs protected the offspring up to 6 weeks old. This suggests that maternal immunization with a mixture of HA and NA DNAs provide the most effective protection against the virus challenge for the offspring of mice.

Animals↗

PubMed2005

Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection.

Understanding gene expression by bacteria during the actual course of human infection may provide important insights into microbial pathogenesis. In this study, we evaluated the transcriptional profile of Vibrio cholerae, the causative agent of cholera, in clinical specimens from cholera patients. We collected samples of human stool and vomitus that were positive by dark-field microscopy for abundant vibrios and used a microarray to compare gene expression in organisms recovered directly from specimens collected during the early and late stages of human infection. Our results reveal that V. cholerae gene expression within the human host environment differs from patterns defined in in vitro models of pathogenesis. tcpA, the major subunit of the essential V. cholerae colonization factor, was significantly more highly expressed in early than in late stages of infection; however, the genes encoding cholera toxin were not highly expressed in either phase of human infection. Furthermore, expression of the virulence regulators toxRS and tcpPH was uncoupled. Interestingly, the pattern of gene expression indicates that the human upper intestine may be a uniquely suitable environment for the transfer of genetic elements that are important in the evolution of pathogenic strains of V. cholerae. These findings provide a more detailed assessment of the transcriptome of V. cholerae in the human host than previous studies of organisms in stool alone and have implications for cholera control and the design of improved vaccines.

Cholera↗

PubMed2004

The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades.

Myeloid differentiation protein-88 (MyD88) is a signal adaptor protein required for cytokine production following engagement of Toll-like receptors (TLRs) by their cognate ligands. Activation of both TLR-3 and TLR-4, however, can engage signaling events independent of MyD88 expression. The relative importance of these MyD88-dependent and -independent signaling pathways in the macrophage response to lipopolysaccharide (LPS) is unknown. Here we define these events using microarray expression profiling of LPS-stimulated macrophages taken from MyD88-null and wild-type mice. Of the 1,055 genes found to be LPS responsive, only 21.5% were dependent on MyD88 expression, with MyD88-independent genes constituting 74.7% of the genetic response. This MyD88-independent gene expression was predominantly transcriptionally regulated, as it was unaffected by cycloheximide blockade of new protein synthesis. A previously undescribed group of LPS-regulated genes (3.8%), whose induction or repression was significantly greater in the absence of MyD88, was also identified by these studies. The regulation of these genes suggested that MyD88 could serve as a molecular brake, constraining gene activity in a subset of LPS-responsive genes. The findings generated with LPS stimulation were recapitulated by exposure of macrophages to live Escherichia coli. These expression-profiling studies redefine the current dogma of TLR-4 signaling and establish that MyD88, although essential for some of the best-characterized macrophage responses to LPS, is not required for the regulation of the majority of genes engaged by macrophage exposure to endotoxin or live bacteria.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Estimating the repeat structure and length of DNA sequences using L-tuples.

In shotgun sequencing projects, the genome or BAC length is not always known. We approach estimating genome length by first estimating the repeat structure of the genome or BAC, sometimes of interest in its own right, on the basis of a set of random reads from a genome project. Moreover, we can find the consensus for repeat families before assembly. Our methods are based on the l-tuple content of the reads.

Algorithms↗