Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation

Abstract

A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre-and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9 and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9 by the histone methyltransferase G9a was not affected by Set9 methylation of H3-K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in transcription activation by competing with histone deacetylases and by precluding H3-K9 methylation by Suv39h1. Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…SET domains are seen in chromosomal proteins that are involved in epigenetic control of gene expression [137]. Early studies revealed that SET7 activates transcription by preventing chromatin condensation [138,139]. Importantly, SET7 can methylate specific lysines on non-histone proteins including transcriptional factors and regulators like p53 and TAF10.…”

Regulation of chromatin by histone modifications

“…They can also function to disrupt an interaction between the histone and a chromatin factor. For instance, H3K4me3 can prevent the NuRD complex from binding to the H3 N-terminal tail [79,80]. This simple mechanism seems to make sense because NuRD is a general transcriptional repressor and H3K4me3 is a mark of active transcription.…”

A Transcriptome-Based Characterization of Habituation in Plant Tissue Culture

“…In transcriptionally silent heterochromatin, for example, DNA methylation is often accompanied by Histone 3 methylation of Lys-9 (H3K9met), as well as Histone 4 hypoacetylation. In transcriptionally active euchromatin, on the other hand, acetylation of Histone 4 is often accompanied by demethylation of H3K9 and methylation of H3K4 (Nishioka et al, 2002;Peters et al, 2002;Hashimshony et al, 2003). The up-regulation of several transposon-related elements and chromatin remodeling factors (At4g31900, At1g80740, At1g69770; Supplemental Table IV) in habituated callus cultures warranted a scan of the expression levels of DNA and histone modification enzymes in T87 habituated calli.…”