title: Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.
abstract: Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Philipp
authors: P
authors: Tropberger
authors: Sebastian
authors: S
authors: Pott
authors: Claudia
authors: C
authors: Keller
authors: Kinga
authors: K
authors: Kamieniarz-Gdula
authors: Matthieu
authors: M
authors: Caron
authors: Florian
authors: F
authors: Richter
authors: Guohong
authors: G
authors: Li
authors: Gerhard
authors: G
authors: Mittler
authors: Edison T
authors: ET
authors: Liu
authors: Marc
authors: M
authors: Bühler
authors: Raphael
authors: R
authors: Margueron
authors: Robert
authors: R
authors: Schneider
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D056890:Eukaryota / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D011960:Receptors, Estrogen; D050880:p300-CBP Transcription Factors