Sunday 15 June 2014

Histone marks

Activating (H3K4me3, H3K4me1, H3K27ac) and repressive histone marks (H3K27me3).

H3K4me3, a hallmark of active promoters (Hon et al. 2009). Two states at active proximal regions are further differentiated by the presence or absence of the H3K27me3 histone modification as (1) active promoters (no H3K27me3) and (2) bivalent promoters (with H3K27me3).

Cited from "tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis" doi: 10.1101/gr.168930.113

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Cited from the paper "The diverse functions of Dot1 and H3K79 methylation"

"One of the covalent histone modifications is methylation, which takes place on both lysine (K) and arginine (R) residues (Zhang and Reinberg 2001; Martin and Zhang 2005). Lysine methylation exists in mono, di, and tri states, while arginine methylation only occurs in mono and di states. One way that these methyl marks contribute to transcriptional regulation is to serve as a platform for the recruitment of effector proteins. The well-studied lysine methylation residues include K4, K9, K27, K36, and K79 of histone H3, and K20 of histone H4. In general, methylation at H3K9, H3K27, and H4K20 correlates with transcriptional repression, while methylation at H3K4, H3K36, and H3K79 correlates with gene transcription (Kouzarides 2002; Peterson and Laniel 2004; Martin and Zhang 2005). In addition to its role in transcriptional regulation, methylation has also been linked to X inactivation, cell fate determination, terminal differentiation, and the spatiotemporal patterning of Hox genes (Cavalli 2006; Minard et al. 2009). Moreover, aberrant histone methylation has also been linked to various human cancers (Feinberg et al. 2002; Handel et al. 2010)."

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"Replacement of canonical histones for H3.3/H2A.Z must be dependent on the recruitment of specific histone chaperones, perhaps by DNA sequence-specific bound transcription factors."

Enhancer function: new insights into the regulation of tissue-specific gene expression

H3K27 Modification

"Embryonic stem cells reflect an early stage of mammalian development and possess a unique chromatin landscape in which 'bivalent' domains of trimethylated histone H3 Lys4 (H3K4me3) and Lys27 (H3K27me3) mark key lineage-specific genes1, 2. Histone H3K4me3 and H3K27me3 are normally associated with active and repressed genes, respectively; however, the promoters of the genes carrying both of these marks simultaneously, 'bivalent promoters', are transcribed at very low levels and are considered to be poised for activation by developmental signals3, 4."

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