H3K4 tri-methylation breadth at transcription start sites impacts the transcriptome of systemic lupus erythematosus

Clinical Epigenetics
Zhe ZhangKathleen E Sullivan

Abstract

The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with modified tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is a canonical chromatin mark of active transcription. Recent studies have suggested that H3K4me3 breadth has an important regulatory role in cell identity. This project examined H3K4me3 breadth at transcription start sites (TSS) in primary monocytes and its association with differential gene transcription in SLE. Integrative analysis was applied to chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data generated from primary monocytes as well as genomic data available in public repositories. Four distinctive H3K4me3 patterns of ChIP-seq peaks were identified at 8399 TSSs. Narrow peaks were highly enriched with genes related to housekeeping functions. The broader peaks with extended H3K4me3 immediately upstream and/or downstream of TSS were associated with immune response genes. Many TSSs had downstream H3K4me3 extended to ~650 bp, where the transition of H3K4me3 to H3K36me3, a transcriptional elongation mark, is often found. The H3K4me3 pattern was strongly associated with transcription in SLE. Genes with narr...Continue Reading

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Jul 14, 2016·Epigenomics·Dashzeveg Bayarsaihan
Oct 26, 2016·Journal of Autoimmunity·Hai LongQianjin Lu
Dec 3, 2016·Arthritis Research & Therapy·Joyce S Hui-YuenJames N Jarvis
Mar 28, 2017·Digestive Diseases and Sciences·Jianzhong YeLanjuan Li
Apr 20, 2019·Nature Reviews. Rheumatology·Laura T DonlinLionel B Ivashkiv
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Aug 23, 2017·Expert Opinion on Therapeutic Targets·Heng LiJianping Zuo
Mar 9, 2018·Frontiers in Immunology·Rob J W ArtsMihai G Netea

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Datasets Mentioned

BETA
GSE58310

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
RNA-seq
histone acetylation

Software Mentioned

IPA
Tophat2
Cuffdiff
Amazon Web Service
Cufflinks
Cuffmerge

Related Concepts

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