Segert, J. A. | Search bioRxiv

bioRxiv2025

Histone H4 lysine 20 monomethylation is not a mark of transcriptional silencers

Transcriptional silencers are cis-regulatory elements that downregulate the expression of target genes. Although thousands of silencers have been identified experimentally, a predictive chromatin signature of silencers has not been found. H4K20me1 previously was reported to be highly enriched among human silencers, but our reanalysis of the data using an appropriate background revealed that the enrichment is only marginal. We generated H4K20me1 ChIP-seq profiles in Drosophila S2 cells, which similarly showed that H4K20me1 does not mark Drosophila silencers and instead is associated with active transcription. Silencers remain a poorly annotated, difficult to predict class of cis-regulatory elements whose specific chromatin features remain to be identified.

genomics↗

bioRxiv2018

Genetic And Epigenetic Fine Mapping Of Complex Trait Associated Loci In The Human Liver

Deciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory regions of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the impacts of genetic variation that direct histone modification states in the liver are poorly understood. Here, we generate the most comprehensive genome-wide dataset of two epigenetic marks, H3K4me3 and H3K27ac, and annotate thousands of putative regulatory elements in the human liver. We integrate these findings with genome-wide gene expression data collected from the same human liver tissues and high-resolution promoter-focused chromatin interaction maps collected from human liver-derived HepG2 cells. We demonstrate widespread functional consequences of natural genetic variation on putative regulatory element activity and gene expression levels. Leveraging these extensive datasets, we fine-map a total of 77 GWAS loci that have been associated with at least one complex phenotype. Our results contribute to the repertoire of genes and regulatory mechanisms governing complex disease development and further the basic understanding of genetic and epigenetic regulation of gene expression in the human liver tissue.

genetics↗