Drosophila HP1c Is Regulated by an Auto-Regulatory Feedback Loop through Its Binding Partner Woc

Abel, Jochen; Eskeland, Ragnhild; Raffa, Grazia D.; Kremmer, Elisabeth; Imhof, Axel

doi:10.1371/journal.pone.0005089

Cited by 24 publications

(24 citation statements)

References 40 publications

(48 reference statements)

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“…We and others previously reported that dHP1c interacts with the transcription factors WOC and ROW 17,18 . Here to identify partners of the dHP1c complex, we performed affinity purifications using stable S2 cell lines expressing ROW-TAP and TAP-WOC fused proteins.…”

mentioning

confidence: 69%

“…7). Finally, it was reported that dHP1c interacts with RNA pol II [17][18][19] , suggesting that binding of the dHP1c complex might depend on RNA pol II. However, arguing against this possibility, we observed that binding of the complex at promoters is resistant to treatment with Actinomycin D (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

“…dDsk2 is highly evolutionarily conserved from yeast to humans 10,15,16 . We show that, in addition to regulating protein stability, Drosophila dDsk2 interacts with the complex formed by the euchromatic dHP1c isoform and the transcription factors WOC and ROW [17][18][19] , localizes at promoters and is required for transcription via nonproteolytic mechanisms.…”

mentioning

confidence: 99%

“…The dHP1c complex was shown to localize at active chromatin domains, suggesting a role in gene expression regulation 17,18 . However, its actual genomic distribution and the extent of overlapping of its components were not known.…”

mentioning

confidence: 99%

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dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

et al. 2015

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dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here we report that dDsk2 plays a nonproteolytic function in transcription regulation. dDsk2 interacts with the dHP1c complex, localizes at promoters of developmental genes and is required for transcription. Through the ubiquitin-binding domain, dDsk2 interacts with H2Bub1, a modification that occurs at dHP1c complex-binding sites. H2Bub1 is not required for binding of the complex; however, dDsk2 depletion strongly reduces H2Bub1. Co-depletion of the H2Bub1 deubiquitylase dUbp8/Nonstop suppresses this reduction and rescues expression of target genes. RNA polymerase II is strongly paused at promoters of dHP1c complex target genes and dDsk2 depletion disrupts pausing. Altogether, these results suggest that dDsk2 prevents dUbp8/Nonstop-dependent H2Bub1 deubiquitylation at promoters of dHP1c complex target genes and regulates RNA polymerase II pausing. These results expand the catalogue of nonproteolytic functions of ubiquitin receptors to the epigenetic regulation of chromatin modifications.

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mentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

et al. 2015

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“…woc encodes a zinc finger protein that interacts with HP1c and functions both in transcriptional regulation and telomere capping. 44,66,67 Woc is enriched at polytene chromosome telomeres and co-localizes with all euchromatic bands that associate with the initiating form of Pol II. 44 We do not know whether Woc interacts with terminin.…”

Section: The Roles Of Drosophila Nonterminin Proteins Required For Tementioning

confidence: 99%

Terminin: A protein complex that mediates epigenetic maintenance ofDrosophilatelomeres

Raffa¹,

Ciapponi²,

Cenci³

et al. 2011

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dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres

et al. 2017

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Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.

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Drosophila HP1c Is Regulated by an Auto-Regulatory Feedback Loop through Its Binding Partner Woc

Cited by 24 publications

References 40 publications

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

Terminin: A protein complex that mediates epigenetic maintenance ofDrosophilatelomeres

dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres

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