Biology subjects

Tsai, Z. T.-Y.

Publications and source records attributed to Tsai, Z. T.-Y..

3 recordsLinked to original sources

bioRxiv2019

Perinatal exposure to lead results in altered DNA methylation in adult mouse liver and blood: Implications for target versus surrogate tissue use in environmental epigenetics

BackgroundDNA methylation is a critical epigenetic mechanism linking early developmental environment to long-term health. In humans, the extent to which toxicant-induced changes in DNA methylation in surrogate tissues, such as blood, mirror those in the target tissues is unclear. The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET II) consortium was established by the National Institute of Environmental Health Sciences to address the utility of surrogate tissues as proxies for toxicant-induced epigenetic changes in target tissues.\n\nObjectivesThe objective of this study was to investigate the effects of perinatal exposure to a human environmentally relevant level (32 ppm in maternal drinking water) of lead (Pb) on liver and blood DNA methylation in adult male and female mice. We hypothesized that developmental Pb exposure would lead to persistent changes in DNA methylation, and that a subset of differentially methylated loci would overlap between liver and blood.\n\nMethodsEnhanced reduced-representation bisulfite sequencing was used to assess DNA methylation in 5 month old Pb-exposed and control mice. Sex-stratified modeling of differential methylation by Pb exposure was conducted using an established bioinformatics pipeline.\n\nResultsAlthough Pb exposure ceased at 3 weeks of age, we observed thousands of stably modified, sex-specific differentially methylated regions in the blood and liver of Pb-exposed animals, including 44 genomically imprinted loci. In males, we discovered 5 sites that overlapped between blood and liver, and exhibited changes in DNA methylation in the same direction in both tissues.\n\nConclusionsThese data demonstrate that perinatal exposure to Pb induces sex-specific changes in hepatic DNA methylation in adulthood, some of which are also present in blood. Ongoing studies will provide additional exposure-specific insights, and include other epigenetic marks that will enable further refinement of the design and analysis of human studies where target tissues are inaccessible.

genomics↗

bioRxiv2018

The borders of cis-regulatory DNA sequences harbor the divergent transcription factor binding motifs in the human genome

Changes in the cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources that shape the gene regulatory evolution in eukaryotes. However, it is currently unclear how dynamic change of DNA sequences introduce various divergence level of TF binding motifs in the genome over evolutionary time. Here, we estimated the evolutionary divergence level of the TF binding motifs, and quantified their occurrences in the DNase I hypersensitive sites. Results from our in silico motif scan and empirical TF-ChIP (chromatin immunoprecipitation) demonstrate that the divergent motifs tend to be introduced at the borders of the cis-regulatory regions, that are likely accompanied with the expansion through evolutionary time. Accordingly, we propose that an expansion by incorporating divergent motifs within the cis-regulatory regions provides a rationale for the evolutionary divergence of regulatory circuits.

genomics↗

bioRxiv2017

Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs

BackgroundThe regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origin have been proposed: de novo origination from intergenic regions, duplication from long noncoding RNA, and pseudogenization from protein. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudo genized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature that these three scenarios have, accompanied by the need of systematic investigation of lincRNA origination, we conduct a comparative genomics study to investigate the evolution of human lincRNAs.\n\nResultsCombining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to the intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome.\n\nConclusionsWe suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.

bioinformatics↗