how to define cis regulatory elements using histone modifications ChIPseq

Question

[BenHu]

Hello, I have some questions about Histone modifications ChIPseq. 1: why are H3K27ac peaks broad? 2: People use H3K27ac or H3K4me1 peaks to define enhancers. I thought enhancers and promoters are open chromatin regions which are Neucleosome Fragment Regions. Why do we use H3K27ac or H3K4me1 to denote enhancers? 3: It is reasonable to intersect H3K27ac peaks with ATACseq to identify putative transcription factors? Best

Answer 1

[ATpoint]

why are H3K27ac peaks broad

It is not, it is a classical narrow histone mark.

2: People use H3K27ac or H3K4me1 peaks to define enhancers. I thought enhancers and promoters are open chromatin regions which are Neuclesome Fragment Regions. Why do we use H3K27ac or H3K4me1 to denote enhancers?

Please dive into the literature. These marks have been shown in numerous studies to be associated with regulatory elements associated with higher gene expression. Loss of these marks was associated with reduction of gene expression. H3K4me1 is typically considered a proxy for the presence-, and H3K27ac for the active nature of a regulatory element. These histone (modifications) carrying these marks are flanking nucleosome-free regions (what you see in ATAC-seq) therefore you (in many cases) should probably see quite an overlap between ATAC-seq and H3K27ac.

3: It is reasonable to intersect H3K27ac peaks with ATACseq to identify putative transcription factors? Best

Scanning the ATAC-seq regions for motifs overlapping H3K27ac sounds reasonable.

Answer 2

[BenHu]

I really appreciate you.

I found that some literatures that reported H3K27ac peaks being broad.

These histone (modifications) carrying these marks are flanking nucleosome-free regions (what you see in ATAC-seq) therefore you (in many cases) should probably see quite an overlap between ATAC-seq and H3K27ac.

based on your explanation, Not entire histone modification peaks overlap with Nucleosome Fragment Regions. If yes, so it is not accurate to define Enhancer or Promoter regions using histone modification peaks.

Thanks again.