Histone H3 Lysine 4 di-methylation: A novel mark for transcriptional fidelity?

Abstract

Although histone H3 Lysine 4 methylation (H3K4me) is strongly associated with active transcription, an increasing number of arguments indicate its repressive role in gene expression. Recent data in the mammalian and budding yeast systems have provided evidence for H3K4me2 and H3K4me3 tethering histone deacetylase complexes (HDACs) to modulate gene expression. In S. cerevisiae, this regulation is mediated by specific subunits within HDACs that recognize the methylation status of H3K4 allowing chromatin reorganization to attenuate or repress transcription. Albeit we are still a long way from understanding the mechanism and biological consequences, it is becoming clear that H3K4me at certain chromatin loci may prevent aberrant gene expression or modulate transcriptional response. This review will provide a brief overview of a novel interpretation of H3K4me and its outcome on transcription regulation and will suggest future challenges for the field of epigenetics.

Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer

“…H3K4 me3 is considered to be a hallmark for transcriptionally active chromatin, 25 and recent findings suggest that methylated H3K4 acts to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4 me3 via CHD1. 26 We observed an unusually strong increase in the levels of histone H3 lysine 4 dimethylation (H3K4 me2) after activation of transcription via HDAC inhibitors, a modification perceived to be associated with repressive chromatin 27 ; however, this mark has also been found to be enriched in the cis-regulatory regions of active promoters as well as at developmentally poised genes. 28 Furthermore, we observed the loss of an activating mark for transcription, histone lysine 4 monomethylation (H3K4 me), 29 after activation of PGIS in cells.…”

“…In agreement with the current literature, we also observed the presence of a repressive marker H3K9Me2 at the PGIS promoter before activation via HDAC inhibitors, and levels of this histone modification decrease after activation. 27,29 Additional detailed studies of histone post-translational modifications are required to functionally delineate the histone code regulating PGIS expression.…”

Interaction between Endogenous Bacterial Flora and Latent HIV Infection

“…Generally, HMTs catalyze the lysine methylation of histones, which can be linked to either transcriptional activation or repression (66). Methylation of histone 3 at lysine 4 (H3K4), H3K36, and H3K79 has been associated with gene activation, whereas H3K9 and H3K27 methylation has been correlated with gene repression (67).…”

RNA Polymerase II Phosphorylation and Gene Expression Regulation

“…It is mainly found around the transcriptional start site (TSS) contributing to transcription initiation, elongation and RNA processing [264]. Set1 recruitment and H3K4 tri-methylation usually peaks at the promoter and 5' region of a gene, depending on Kin28/Cdk7 activity ( Figure 7) and Paf1 complex, a RNAPII-associated complex [265], and contributes to transcription initiation, elongation and RNA processing [264] [98]. H3K4 mono and di-methylation tend to expand along the coding regions compared to try-methylation.…”

“…HDACs' recruitment is triggered by H3K4 methylation at promoters and within coding regions to restrict hyperactetylated histones to promoters and to maintain transcription activity. Set1-H3K4me2 can be recognized by two different HDACs, RPD3S or SET3C [264]. The Set1-SET3C pathway preferentially affects actively transcribed genes with promoters configured for efficient initiation/re-initiation [269].…”