Is H3K4me3 instructive for transcription activation?

Françoise S Howe,Harry Fischl,Struan C Murray,Jane Mellor

doi:10.1002/bies.201600095

Abstract

Tri-methylation of lysine 4 on histone H3 (H3K4me3) is a near-universal chromatin modification at the transcription start site of active genes in eukaryotes from yeast to man and its levels reflect the amount of transcription. Because of this association, H3K4me3 is often described as an 'activating' histone modification and assumed to have an instructive role in the transcription of genes, but the field is lacking a conserved mechanism to support this view. The overwhelming finding from genome-wide studies is that actually very little transcription changes upon removal of most H3K4me3 under steady-state or dynamically changing conditions, including at mammalian CpG island promoters. Instead, rather than a major role in instructing transcription, time-resolved experiments provide more evidence supporting the deposition of H3K4me3 into chromatin as a result of transcription, influencing processes such as memory of previous states, transcriptional consistency between cells in a population and transcription termination.

Highlights

The overwhelming finding from most genome-wide transcript and transcription studies upon removal of the majority of tri-methylation of lysine on histone H3 (H3K4me3) is that very few transcription events/ mRNAs change at the population level, which is remarkable considering the strong correlations with transcripts and transcription
Rather than a major role in instructing transcription, H3K4me3 may instead be deposited as a result of transcription, influencing processes such as splicing, transcription termination, memory of previous states and transcriptional consistency
One consideration is that because all studies are populationbased, the consequences of the action of H3K4me3 may only be understood at the level of an individual cell

Summary

Review essays

Tri-methylation of lysine 4 on histone H3 (H3K4me3) is a near-universal chromatin modification at the transcription start site of active genes in eukaryotes from yeast to man and its levels reflect the amount of transcription. Because of this association, H3K4me is often described as an activating histone modification and assumed to have an instructive role in the transcription of genes, but the field is lacking a conserved mechanism to support this view. Rather than a major role in instructing transcription, time-resolved experiments provide more evidence supporting the deposition of H3K4me into chromatin as a result of transcription, influencing processes such as memory of previous states, transcriptional consistency between cells in.

Introduction

Number of genes with changes

Associated consequence of interaction

Findings

Concluding remarks