Regulation of chromatin by histone modifications

Abstract

Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

“…Similarly, although we have observed in this study results suggesting a potential mechanism for the overexpression of ARG2 and AMD1 in suicide completers, further research is necessary to find the exact action of DNA methylation on these genes. It is also possible that the expression of these genes is regulated by other epigenetic mechanisms such as non-coding RNAs or other post-translational histone modifications (Bannister & Kouzarides, 2011). Finally, due to the use of post-mortem brain tissue, it is possible that there were confounding post-mortem or clinical variables that were not accounted for in this study.…”

Translating Lung Function Genome-Wide Association Study (GWAS) Findings

“…Histone modifications are also used to identify the location of other functional elements such as enhancers (Shlyueva, Stampfel, & Stark, 2014). The above list is not exhaustive of all possible histone modifications and a detailed description of the majority of known histone modifications can be found reviewed in (Bannister & Kouzarides, 2011). Because the majority of SNPs in GWAS studies are non-coding and aberrant gene regulation is thought to play a predominant role in disease pathogenesis, epigenetic control is likely to take a central stage in functional translation of GWAS findings.…”

Transcriptional activators and activation mechanisms

“…The second mechanism involves posttranslational modifications of histone (Kouzarides, 2007;Li et al, 2007;Ruthenburg et al, 2007;Bannister and Kouzarides, 2011). Histones have flexible, unstructured N-terminal tails that are subject to a variety of posttranslational modifications, including acetylation, phosphorylation, methylation and ubiquitination (Kouzarides, 2007;Li et al, 2007;Ruthenburg et al, 2007;Bannister and Kouzarides, 2011).…”

“…Histones have flexible, unstructured N-terminal tails that are subject to a variety of posttranslational modifications, including acetylation, phosphorylation, methylation and ubiquitination (Kouzarides, 2007;Li et al, 2007;Ruthenburg et al, 2007;Bannister and Kouzarides, 2011). It is thought that many of these modifications, in particular acetylation, can reduce the net positive charge of nucleosomes, thus loosening their interactions with DNA and increasing the efficiency of transcription initiation or elongation .…”