Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • Generally histone modifications facilitate protein protein i

    2018-11-06

    Generally, histone modifications facilitate protein–protein interactions with effector proteins or readers. Bromodomains interact with acetyl-lysines, while chromodomains, plant homeodomains (PHD), and others associate with methyl-lysines. Interestingly, H2AZ-containing nucleosomes associate with several potential readers, including the chromodomain protein CHD3 (MI-2) (Fujimoto et al., 2012) and the bromodomain protein BRD2 (Draker et al., 2012).
    H2AZ genome-wide Genome-wide localisation experiments in protozoa, fungi, animals, and plants (Creyghton et al., 2008; Albert et al., 2007; Guillemette et al., 2005; Li et al., 2005; Petter et al., 2011; Raisner et al., 2005; Siegel et al., 2009; Whittle et al., 2008; Zilberman et al., 2008) demonstrate that H2AZ is highly enriched within the few nucleosome surrounding transcriptional start sites (TSS). In agreement with Valdés-Mora et al., who showed that H2AZac is solely found at the TSS of actively transcribed genes (Valdés-Mora et al., 2012), H2AZac is distributed at H3K27me3-depleted promoters (Hu et al., 2013). In addition, the level of H2AZac also correlates with levels of gene expression in v6.5 mES TAPI-1 Supplier (Ku et al., 2012). Genome-wide ChIPseq surveys of H2AZ-containing nucleosomes in human and mouse ES cells show that H2AZ is enriched at promoters, enhancers, and intergenic regions marked by H3K4me3, as well as bivalent promoters marked by H3K27me3 and H3K4me3 (Ku et al., 2012), in agreement with previous studies (Creyghton et al., 2008; Illingworth et al., 2012). Interestingly, in v6.5 mES cells the H3K4me3/H3K27me3 bivalent domains contain the H2AZac/ub dual mark (Ku et al., 2012). Remarkably, H2AZub is portrayed as a silencing mark (Draker et al., 2011; Sarcinella et al., 2007), while H2AZac is associated with transcriptional activity (Bruce et al., 2005; Valdés-Mora et al., 2012), suggesting that bivalent domains are marked by antagonistic modifications on both H3 (H3K4me3 versus H3K27me3) and H2AZ (H2AZac versus H2AZub1).
    H2AZ at enhancers Enhancer regions underlay regulatory processes by which cells establish patterns of gene expression. In particular, the H2AZ and H3K4me1 marks are deposited at enhancer regions throughout the genome. The H2AZ mark has been used to identify tens of thousands of enhancers in hematopoietic stem and progenitor (HSP) cells and differentiated cell types. Remarkably, H2AZ was used to identify functional enhancers specific for distinct hematopoietic cell types. Specifically, in HSP cells, H2AZ was incorporated at specific enhancers with H3K4me1, but in differentiated B or T cells, the H2AZ and H3K4me1 marks were replaced by H3K27me3. Genome-wide, H2AZ is found at H3K4me3-marked enhancers in both human and mouse ES cells (Ku et al., 2012). At the gene level, H2AZ is found at the downstream enhancer of CCND1 and is evicted upon estradiol-induced gene expression (Dalvai et al., 2013). Chromatin conformation capture (3C) studies at the CCDN1 locus reveal that the downstream enhancer interacts with the TSS and that these interactions are lost upon activation of transcription (Dalvai et al., 2013). In the absence of TIP48, the enhancer and TSS still interact, but upon estradiol induction of transcription, the two regions retain high level of interactions (Dalvai et al., 2013), suggesting that TIP48 is required for chromatin remodelling and disrupting the interactions between the enhancer and the TSS of CCND1 upon gene activation.
    Concluding remark The current emerging picture is that similarly to canonical histones, H2AZ biological functions are regulated by post-translational modifications. It is thus tempting to speculate that H2AZac, H2AZK7me1, H2AZK4me1K7me1, and H2AZK121ub mediate protein–protein interactions with as yet unidentified histone mark readers to convey chromatin signaling.
    Acknowledgments OB is supported by the Newcastle\'s Biomedical Fellowship Programme, which is in part funded through the Wellcome Trust\'s Institutional Strategic Support Fund.