DNase I–hypersensitive exons colocalize with promoters and distal regulatory elements

Mercer, Tim R.; Edwards, Stacey L.; Clark, Michael B.; Neph, Shane; Wang, Hao; Stergachis, Andrew B.; John, Sam; Sandstrom, Richard; Li, Guo Liang; Sandhu, Kuljeet Singh; Ruan, Yijun; Nielsen, Lars K.; Mattick, John S.; Stamatoyannopoulos, J

doi:10.1038/ng.2677

Cited by 117 publications

(127 citation statements)

References 59 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Interestingly, the later set of genes contained multiple active enhancers within their gene bodies in DKO1 cells, and these same enhancers were methylated in HCT116 cells. Intronic enhancers have been previously described to regulate the genes they reside within [23,[31][32][33]. Here, we have identified several hundred genes that may be controlled by increases in active histones at intragenic enhancers.…”

Section: Discussionmentioning

confidence: 87%

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

et al. 2014

View full text Add to dashboard Cite

Background: Gene expression is epigenetically regulated by a combination of histone modifications and methylation of CpG dinucleotides in promoters. In normal cells, CpG-rich promoters are typically unmethylated, marked with histone modifications such as H3K4me3, and are highly active. During neoplastic transformation, CpG dinucleotides of CG-rich promoters become aberrantly methylated, corresponding with the removal of active histone modifications and transcriptional silencing. Outside of promoter regions, distal enhancers play a major role in the cell type-specific regulation of gene expression. Enhancers, which function by bringing activating complexes to promoters through chromosomal looping, are also modulated by a combination of DNA methylation and histone modifications.

show abstract

Section: Discussionmentioning

confidence: 87%

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…1D). Although the function of H3K27me3 in gene bodies remains unclear, recent studies have suggested that it may be related to alternative promoter use (18), alternative splicing (19,20), or monoallelic gene expression (21). Long noncoding RNAs have recently been implicated in gene regulation and Polycomb recruitment (22,23).…”

Section: Resultsmentioning

confidence: 99%

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Pinello

Orkin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Chromatin states are highly cell-type-specific, but the underlying mechanisms for the establishment and maintenance of their genome-wide patterns remain poorly understood. Here we present a computational approach for investigation of chromatin-state plasticity. We applied this approach to investigate an ENCODE ChIP-seq dataset profiling the genome-wide distributions of the H3K27me3 mark in 19 human cell lines. We found that the high plasticity regions (HPRs) can be divided into two functionally and mechanistically distinct subsets, which correspond to CpG island (CGI) proximal or distal regions, respectively. Although the CGI proximal HPRs are typically associated with continuous variation across different cell-types, the distal HPRs are associated with binary-like variations. We developed a computational approach to predict putative cell-type-specific modulators of H3K27me3 patterns and validated the predictions by comparing with public ChIPseq data. Furthermore, we applied this approach to investigate mechanisms for poised enhancer establishment in primary human erythroid precursors. Importantly, we predicted and experimentally validated that the principal hematopoietic regulator T-cell acute lymphocytic leukemia-1 (TAL1) is involved in regulating H3K27me3 variations in collaboration with the transcription factor growth factor independent 1B (GFI1B), providing fresh insights into the context-specific role of TAL1 in erythropoiesis. Our approach is generally applicable to investigate the regulatory mechanisms of epigenetic pathways in establishing cellular identity.polycomb | hematopoiesis | histone modifications | motifs

show abstract

“…133 DNase I hypersensitive sites are also a mark of open chromatin regions containing promoters and enhancers. 134 Assay for transposase-accessible chromatin with highthroughput sequencing is a useful method for measuring chromatin accessibility genome wide. 135 An important caveat is that these analyses require genome-wide chromatin data from a relevant cell type.…”

Section: From Locus To Functionmentioning

confidence: 99%

Genetics of Coronary Artery Disease

McPherson

Tybjærg‐Hansen

2016

Circulation Research

327

203

View full text Add to dashboard Cite

Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing >200 000 individuals complemented by bioinformatic approaches, including 1000 Genomes imputation, expression quantitative trait locus analyses, and interrogation of Encyclopedia of DNA Elements, Roadmap, and other data sets. close to 60 common SNPs (minor allele frequency>0.05) associated with CAD risk and reaching genomewide significance (P<5×10 −8 ) have been identified. Furthermore, a total of 202 independent signals in 109 loci have achieved a false discovery rate (q<0.05) and together explain 28% of the estimated heritability of CAD. These data have been used successfully to create genetic risk scores that can improve risk prediction beyond conventional risk factors and identify those individuals who will benefit most from statin therapy. Such information also has important applications in clinical medicine and drug discovery by using a Mendelian randomization approach to interrogate the causal nature of many factors found to associate with CAD risk in epidemiological studies. In contrast to genome-wide association studies, whole-exome sequencing has provided valuable information directly relevant to genes with known roles in plasma lipoprotein metabolism but has, thus far, failed to identify other rare coding variants linked to CAD. Overall, recent studies have led to a broader understanding of the genetic architecture of CAD and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on CAD risk. Despite this success, there has been limited progress in understanding the function of the novel loci; the majority of which are in noncoding regions of the genome. (Circ Res. 2016;118:564-578.

show abstract

DNase I–hypersensitive exons colocalize with promoters and distal regulatory elements

Cited by 117 publications

References 59 publications

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Genetics of Coronary Artery Disease

Contact Info

Product

Resources

About