H3K9 histone methyltransferase G9a‐mediated transcriptional activation of p21

Abstract

Edited by Angel NebredaKeywords: G9a p21 Transcription Apoptosis Etoposide a b s t r a c tWe report that H3K9 HMTase G9a activates transcription of the cell cycle regulatory gene, p21, in p53-null H1299 cells. Positive regulation of p21 by G9a is independent of its HMTase activity. We demonstrate that G9a upregulates p21 via interaction with PCAF, and provide evidence that the activating complex is recruited to the p21 promoter upon DNA damage-inducing agent etoposide treatment. Our study suggests that G9a decreases proliferation and cell viability by increasing the level of p21-mediated apoptosis. Our results suggest that G9a functions as a coactivator for p21 transcription, and directs cells to undergo apoptosis. Structured summary of protein interactions:G9a physically interacts with PCAF by anti tag coimmunoprecipitation (1, 2) G9a physically interacts with PCAF by anti bait coimmunoprecipitation (View interaction)

A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin

“…The G9a catalytic domain is sufficient for silencing a target reporter gene (66,67); however, G9a promotes DNA methylation through its ankyrin repeat domain independently of its lysine methylation activity (13, 68 -71). Furthermore, the catalytic activity of G9a is dispensable for transcriptional activation of several genes (49,50,(52)(53)(54), and G9a has a number of non-histone substrates, including itself, which would be affected by enzymatic inhibition but potentially not a knockdown of WIZ (17)(18)(19)(20)(21). Our results confirmed that catalytic activity was dispensable for the regulation of a subset of genes on our microarray (Fig.…”

The expanding role of the Ehmt2/G9a complex in neurodevelopment

“…45 Ehmt2 has been shown to be essential for activation of several genes critical to early development including p21 46 and b-Globin. 47 Unlike transcriptional repression, Ehmt2's co-activator role does not require either the SET or Ank repeat domains, 6,46,48 suggesting that this coactivator role is methylation-independent. Furthermore, Ehmt2 is dependent upon a different pool of transcription factors, such as Runx2 49 and Nfe2, 47 to recruit it to sites of transcriptional activation.…”

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

“…G9a mediates gene repression by di-methylating lysine 9 of the histone H3 (H3K9me2), and by scaffolding the interaction of repressor protein complexes at target genes (Shinkai and Tachibana, 2011;Tachibana et al, 2002). In addition, G9a also co-activates gene expression through interaction with histone acetyl transferase complexes (Oh et al, 2014) and estrogen receptors (Purcell et al, 2011). G9a is required for embryonic development.…”