Protein Complex of Drosophila ATRX/XNP and HP1a Is Required for the Formation of Pericentric Beta-heterochromatin in Vivo

Emelyanov, Alexander; Konev, Alexander Y.; Vershilova, Elena; Fyodorov, Dmitry V.

doi:10.1074/jbc.m109.064790

Cited by 34 publications

(41 citation statements)

References 48 publications

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“…4A, panels 2 to 5). As previously described (18)(19)(20), we also observed that animals with reduced xnp function (xnp 56 /ϩ) or lacking xnp function (xnp 56 /xnp 56 ) display derepressed w expression (Fig. 4A, panels 6 and 7).…”

Section: Resultssupporting

confidence: 84%

“…Previous studies have shown that loss-offunction alleles of xnp affect fly viability (18)(19)(20). We similarly observed that the development of both xnp 56 /Df(3R)Exel6202 and homozygous xnp 56 embryos is affected, leading to reduced viability (Table 1).…”

Section: Resultssupporting

confidence: 73%

“…Surprisingly, XNP (18)(19)(20), the Drosophila counterpart of ATRX, was not found among the proteins associated with e-H3.3, whereas DAXX and ATRX physically interact and belong to the e-H3.3 preassembly complex isolated from HeLa cells (11). The absence of XNP in immunopurified H3.3 and H3 complexes was confirmed by immunoblotting ( Fig.…”

Section: Resultsmentioning

confidence: 89%

“…(16,17). XNP, the Drosophila homolog of ATRX, is not essential, and XNP-deficient flies are viable and fertile (18)(19)(20). This suggests that H3.3 assembly factors may be redundant, or alternatively, there may be additional factors involved in H3.3 deposition.…”

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confidence: 99%

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The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation

Fromental-Ramain

Ramain

Hamiche

2017

Molecular and Cellular Biology

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Histone variants are nonallelic isoforms of canonical histones, and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/␣-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of the Drosophila DAXX-like protein (DLP) by using both fly genetic approaches and protein biochemistry. DLP specifically interacts with H3.3 and shows a prominent localization on the base of the X chromosome, where it appears to act in concert with XNP, the Drosophila homolog of ATRX, in heterochromatin assembly and maintenance. The functional association between DLP and XNP is further supported by a series of experiments that illustrate genetic interactions and the DLP-XNP-dependent localization of specific chromosomal proteins. In addition, DLP both participates in the RI deposition of H3.3 and associates with anti-silencing factor 1 (ASF1). We suggest, in agreement with a recently proposed model, that DLP and ASF1 are part of a predeposition complex, which is recruited by XNP and is necessary to prevent DNA exposure in the nucleus.KEYWORDS DLP, heterochromatin, histone variant, H3.3, XNP, ASF1 I n the nucleus, DNA is packaged under the form of chromatin. The basic repeating unit of chromatin is the nucleosome, and the nucleosome core particle consists of approximately 146 bp of DNA wrapped around a histone octamer composed of two copies of each of the histones H2A, H2B, H3, and H4. (1, 2). Gene-rich domains are packaged into euchromatin, which is decondensed in interphase nuclei and is enriched for histone modifications characteristic of transcriptionally active regions. Moreover, euchromatin often exhibits high DNA accessibility. In contrast, gene-poor domains and repetitive sequences are packaged into condensed heterochromatin that carries histone modifications associated with transcriptional repression.In addition to the canonical core histones, cells express nonallelic-isoform histone variants (3). Histone variants have emerged as essential contributors to the regulation of chromatin structure, and they are involved in multiple processes, including chromatin stability, DNA repair, and transcriptional regulation. Canonical histones are almost exclusively expressed during the S phase of the cell cycle and are incorporated into chromatin in a DNA replication-dependent fashion, whereas replication-independent (RI) histone variants are expressed throughout the cell cycle.One of the best-studied histone variants is H3.3, which can replace the major species H3 (4). H3.3 is expressed and incorporated at all phases of the cell cycle (5). The available data suggest that H3.3 is a marker of active chromatin and associated with the

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Section: Resultssupporting

confidence: 84%

Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 89%

mentioning

confidence: 99%

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The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation

Fromental-Ramain

Ramain

Hamiche

2017

Molecular and Cellular Biology

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“…Recombinant Proteins-Recombinant Drosophila His 6 -Su-(var)3-9 and FLAG-HP1 proteins were purified as described (40,41). Full-length Drosophila H1 and truncated H1 polypeptides were cloned into NdeI and SalI sites of pET24-iCBD vector in-frame with intein and chitin binding domain.…”

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confidence: 99%

Independent Biological and Biochemical Functions for Individual Structural Domains of Drosophila Linker Histone H1

Kavi¹,

Emelyanov

Fyodorov

et al. 2016

Journal of Biological Chemistry

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Linker histone H1 is among the most abundant components of chromatin. H1 has profound effects on chromosome architecture. H1 also helps to tether DNA-and histone-modifying enzymes to chromatin. Metazoan linker histones have a conserved tripartite structure comprising N-terminal, globular, and long, unstructured C-terminal domains. Here we utilize truncated Drosophila H1 polypeptides in vitro and H1 mutant transgenes in vivo to interrogate the roles of these domains in multiple biochemical and biological activities of H1. We demonstrate that the globular domain and the proximal part of the C-terminal domain are essential for H1 deposition into chromosomes and for the stability of H1-chromatin binding. The two domains are also essential for fly viability and the establishment of a normal polytene chromosome structure. Additionally, through interaction with the heterochromatin-specific histone H3 Lys-9 methyltransferase Su(var)3-9, the H1 C-terminal domain makes important contributions to formation and H3K9 methylation of heterochromatin as well as silencing of transposons in heterochromatin. Surprisingly, the N-terminal domain does not appear to be required for any of these functions. However, it is involved in the formation of a single chromocenter in polytene chromosomes. In summary, we have discovered that linker histone H1, similar to core histones, exerts its multiple biological functions through independent, biochemically separable activities of its individual structural domains.DNA in the eukaryotic nucleus is packaged into a compact nucleoprotein complex called chromatin (1, 2). The histones constitute a family of basic proteins that play a vital role in organizing chromatin. There are five major classes of histones: the core histones H2A, H2B, H3, and H4 and the linker histone H1. The nucleosome core particle, the fundamental unit of chromatin, consists of an octamer of two copies of each of the core histones around which about 146 bp of DNA is wrapped. H1 binds to the nucleosome core particle and the linker DNA between adjacent core particles. The stoichiometry of H1 to nucleosome core particles in cells of complex eukaryotes ranges from about 0.5 to approximately equimolar (3). Given this abundance, the linker histone H1 is expected to play important roles in chromatin structure. Indeed, numerous in vitro studies, as well as experiments in vivo, have shown that H1 has a profound effect on chromatin structure (reviewed in Refs. 4 and 5). For example, incorporation of H1 into chromatin leads to an increase in the spacing between nucleosome core particles. H1 also facilitates the folding of chromatin into more compact structures. In addition to these architectural roles, there are now an increasing number of reports describing interactions between H1 linker histones and a variety of other nuclear proteins (6), including functional interactions between H1, histone-modifying enzymes, and DNA methyltransferases that lead to modulation of epigenetic marking of chromatin (7,8). In this context, it is notable th...

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Chromatin Structure and ATRX Function in Mouse Oocytes

Fuente

Baumann

Viveiros

2012

Results and Problems in Cell Differentiation

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Differentiation of chromatin structure and function during oogenesis is essential to confer the mammalian oocyte with meiotic and developmental potential. Errors in chromosome segregation during female meiosis and subsequent transmission of an abnormal chromosome complement (aneuploidy) to the early conceptus are one of the leading causes of pregnancy loss in women. The chromatin remodeling protein ATRX (α-thalassemia mental retardation X-linked) has recently emerged as a critical factor involved in heterochromatin formation at mammalian centromeres during meiosis. In mammalian oocytes, ATRX binds to centromeric heterochromatin domains where it is required for accurate chromosome segregation. Loss of ATRX function induces abnormal meiotic chromosome morphology, reduces histone H3 phosphorylation, and promotes a high incidence of aneuploidy associated with severely reduced fertility. The presence of centromeric breaks during the transition to the first mitosis in the early embryo indicates that the role of ATRX in chromosome segregation is mediated through an epigenetic mechanism involving the maintenance of chromatin modifications associated with pericentric heterochromatin (PCH) formation and chromosome condensation. This is consistent with the existence of a potential molecular link between centromeric and PCH in the epigenetic control of centromere function and maintenance of chromosome stability in mammalian oocytes. Dissecting the molecular mechanisms of ATRX function during meiosis will have important clinical implications towards uncovering the epigenetic factors contributing to the onset of aneuploidy in the human oocyte.

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Protein Complex of Drosophila ATRX/XNP and HP1a Is Required for the Formation of Pericentric Beta-heterochromatin in Vivo

Cited by 34 publications

References 48 publications

The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation

The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation

Independent Biological and Biochemical Functions for Individual Structural Domains of Drosophila Linker Histone H1

Chromatin Structure and ATRX Function in Mouse Oocytes

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