The composition and organization of Drosophila heterochromatin are heterogeneous and dynamic

Swenson, Joel M.; Colmenares, Serafin U.; Strom, Amy R.; Costes, Sylvain V.; Karpen, Gary H.

doi:10.7554/elife.16096

Cited by 65 publications

(76 citation statements)

References 168 publications

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“…However the mechanisms linking these silencing pathways are not fully understood and it is clear that factors involved in heterochromatin formation and function remain to be identified. For example a recent study of HP1a interactors in Drosophila identified many new factors needed for gene silencing and/or heterochromatin organization (73)…”

Section: Discussionmentioning

confidence: 99%

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

McMurchy

Stempor

Gaarenstroom

et al. 2017

Preprint

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Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.

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Section: Discussionmentioning

confidence: 99%

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

McMurchy

Stempor

Gaarenstroom

et al. 2017

Preprint

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“…XNP lacks the C-terminal plant homeodomain (PHD) fingers that are present in ATRX and that mediate ATRX binding to chromatin. In Drosophila, interaction with chromatin is achieved by a separate protein, called dADD1 (32). Mass spectrometry analysis revealed that dADD1, similarly to XNP, was not found among the proteins present in the immunopurified H3.3 complexes.…”

Section: Resultsmentioning

confidence: 99%

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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“…Our work raises questions 443 about the biological significance of SUUR binding to heterochromatin, since without the SNF2 444 domain SUUR is still constitutively bound to heterochromatin, yet unable to induce 445 underreplication. Additionally, SUUR dynamically associates with heterochromatin in mitotic 446 cells although heterochromatin is fully replicated (Swenson et al, 2016). 447 448…”

Section: Snf2 Domain and Fork Localization 420mentioning

confidence: 99%

Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila

Munden

Rong

Gangula

et al. 2018

Preprint

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Control of DNA copy number is essential to maintain genome stability and ensure proper cell and tissue function. In Drosophila polyploid cells, the SNF2-domain-containing SUUR protein inhibits replication fork progression within specific regions of the genome to promote DNA underreplication. While dissecting the function of SUUR’s SNF2 domain, we identified a physical interaction between SUUR and Rif1. Rif1 has many roles in DNA metabolism and regulates the replication timing program. We demonstrate that repression of DNA replication is dependent on Rif1. Rif1 localizes to active replication forks in an SUUR-dependent manner and directly regulates replication fork progression. Importantly, SUUR associates with replication forks in the absence of Rif1, indicating that Rif1 acts downstream of SUUR to inhibit fork progression. Our findings uncover an unrecognized function of the Rif1 protein as a regulator of replication fork progression.

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The composition and organization of Drosophila heterochromatin are heterogeneous and dynamic

Cited by 65 publications

References 168 publications

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

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

Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila

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