In and out: Histone variant exchange in chromatin
ABSTRACT Alterations in nucleosome structure affect the accessibility of the DNA and can generate specialized domains of chromatin in the genome. Such changes can be introduced by posttranslational modifications of histones, by chromatin remodeling, or by the incorporation of variants of H2A and H3 into nucleosomes. In contrast to the canonical histones, which are deposited behind the replication fork during S phase, histone variants are incorporated in a process that is independent of DNA replication. Recent studies have shown that distinct multiprotein complexes are responsible for the targeted deposition of histone variants at active genes, centromeres and silent loci. The incorporation of histone variants most probably has epigenetic consequences and contributes to architectural changes in chromosomes.
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- "This flexible and efficient intercommunication between genomic DNA and exogenous influences can be explained by several epigenetic mechanisms, such as DNA methylation , ATP-dependent chromatin remodeling , non-coding RNAs , post-translational modifications (PTMs) of histones, and the replacement of canonical histones with non-allelic histone variants [10,11]. Among these, the non-random deposition of histone variants into chromatin that occurs independently of DNA replication, substantially contributes to gene regulation and architectural changes in chromosomes . "
ABSTRACT: The specific deposition of histone variants into chromatin is an important epigenetic mechanism that contributes to gene regulation through chromatin architectural changes. The histone variant H2A.Z is essential in higher eukaryotes, and its incorporation within chromatin is a relevant process for gene expression and genome stability. However, the dual positive and negative roles of H2A.Z in gene regulation still remain unclear. We previously reported that acclimatization in common carp fish (Cyprinus carpio) involves cyclical seasonal gene reprogramming as an adaptation response to its natural environment, when rRNA synthesis and processing are profoundly affected. Epigenetic mechanisms primarily contribute to the transcriptional modulation of ribosomal genes concomitant with the acclimatization process, thus significantly regulating this process. The aim of this study was to describe the presence of several H2A.Z subtypes in carp, and assess the role of H2A.Z on the ribosomal cistron in summer- and winter-acclimatized carp. This paper reports for the first time about the transcriptional expression of four different H2A.Z subtypes belonging to the same organism. Remarkably, a novel H2A.Z.7 was found, which corresponds to a tissue-specific histone subtype that contains seven amino acid residues longer than the canonical H2A.Z. Moreover, H2A.Z enrichment through the ribosomal cistron was significantly higher during summer, when rRNA transcription and processing are highly active, than it was in winter. Similar patterns of H2A.Z enrichment are found in two seasonally active promoters for genes transcribed by RNA polymerase II, the L41 and Delta9-desaturase genes. Interestingly, ubiquitylated-H2A.Z (H2A.Zub) was strongly enriched on regulatory regions of the ribosomal cistron in summer-acclimatized carp. Additionally, H2A.Z was present in both heterochromatin and euchromatin states on ribosomal cistron and RNA polymerase II promoters. Our study revealed seasonally-dependent H2A.Z enrichment for active ribosomal cistron and RNA polymerase II promoters during the carp environmental adaptation. Moreover, seasonal H2A.Zub enrichment appears as a specific mechanism contributing to the regulation of chromatin architecture under natural conditions. The existence of several H2A.Z subtypes in carp suggests that the epigenetic regulation in this species constitutes a complex and finely tuned mechanism developed to cope with seasonal environmental changes that occur in its habitat.Epigenetics & Chromatin 07/2013; 6(1):22. DOI:10.1186/1756-8935-6-22 · 4.46 Impact Factor
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- "Depletion of DNp63a leads to loss of H2A.Z and RNA polymerase II (RNAPII) activation Both the SRCAP complex and a smaller subcomplex composed of RUVBL1, RUVBL2, DMAP1, and ACTL6A have been shown to exchange histone H2A with the histone variant H2A.Z (Jin et al. 2005; Choi et al. 2009; Huen et al. 2010; Billon and Cô té 2012). Interestingly, H2A.Z has been previously identified as a transcriptional repressor in some settings (Gé vry et al. 2007; Marques et al. 2010). "
ABSTRACT: ΔNp63α is a member of the p53 family of transcription factors that functions as an oncogene in squamous cell carcinomas (SCCs). Because ΔNp63α and p53 bind virtually identical DNA sequence motifs, it has been proposed that ΔNp63α functions as a dominant-negative inhibitor of p53 to promote proliferation and block apoptosis. However, most SCCs concurrently overexpress ΔNp63α and inactivate p53, suggesting the autonomous action of these oncogenic events. Here we report the discovery of a novel mechanism of transcriptional repression by ΔNp63α that reconciles these observations. We found that although both proteins bind the same genomic sites, they regulate largely nonoverlapping gene sets. Upon activation, p53 binds all enhancers regardless of ΔNp63α status but fails to transactivate genes repressed by ΔNp63α. We found that ΔNp63α associates with the SRCAP chromatin regulatory complex involved in H2A/H2A.Z exchange and mediates H2A.Z deposition at its target loci. Interestingly, knockdown of SRCAP subunits or H2A.Z leads to specific induction of ΔNp63α-repressed genes. We identified SAMD9L as a key anti-proliferative gene repressed by ΔNp63α and H2A.Z whose depletion suffices to reverse the arrest phenotype caused by ΔNp63α knockdown. Collectively, these results illuminate a molecular pathway contributing to the autonomous oncogenic effects of ΔNp63α.Genes & development 09/2012; 26(20):2325-36. DOI:10.1101/gad.198069.112 · 12.64 Impact Factor
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- "Drosophila HOT DNAs share certain sequence features , including GAGA elements (see below) and the TAGteam motif, which binds Zelda (Liang et al. 2008; Satija and Bradley 2012). Like other regions containing these regulatory elements, HOT DNAs exhibit increased nucleosome turnover and histone H3.3, indicative of ''open'' chromatin (Jin et al. 2005). Genes proximal to HOT DNAs exhibit increased transcriptional activity during early development, a common feature of genes containing Zelda sites (Moorman et al. 2006; Satija and Bradley 2012). "
ABSTRACT: Enhancers mediate localized patterns of gene expression during development. A common feature of "traditional" enhancers is the presence of clustered binding motifs for sequence-specific transcription factors (TFs). In this issue of Genes & Development, Kvon and colleagues (pp. 908-913) present new evidence that HOT (highly occupied transcription) DNAs direct specific patterns of gene expression, despite being depleted for TF-binding motifs.Genes & development 05/2012; 26(9):873-6. DOI:10.1101/gad.192583.112 · 12.64 Impact Factor