Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin

Eustermann, Sebastian; Yang, Jiayi; Law, Michael J.; Amos, Rachel; Jelinska, Clare; Chapman, Lynda; Gibbons, Richard J.; Rhodes, Daniela; Higgs, Deborah; Neuhaus, David

doi:10.1107/s0108767311098862

Cited by 41 publications

(80 citation statements)

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“…This comprises a PHDlike zinc finger and an additional C 2 C 2 motif just upstream, which is structurally similar to the GATA1 zinc fingers (Gibbons et al 1997;Argentaro et al 2007) and is highly related to the zinc finger domains of DNA methyltransferases (Argentaro et al 2007). The domain mediates binding to the amino-terminal tail of histone H3 trimethylated at lysine 9 (Dhayalan et al 2011;Eustermann et al 2011;Iwase et al 2011). The functional importance of the ADD segment in ATRX is clear.…”

Section: Characterization Of the Atrx Gene And Its Protein Productmentioning

confidence: 99%

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Gibbons

2012

Cold Spring Harbor Perspectives in Medicine

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Section: Characterization Of the Atrx Gene And Its Protein Productmentioning

confidence: 99%

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Gibbons

2012

Cold Spring Harbor Perspectives in Medicine

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“…3A,B). ATRX(1-1201), which includes the ADD domain, an atypical histone H3-lysine 9 trimethylation binding module required for ATRX recruitment to pericentric heterochromatin (Eustermann et al, 2011;Iwase et al, 2011), was not enriched suggesting that histone modifications do not recruit ATRX to the array (Fig. 3A,B, panels a-d).…”

Section: The Atrx Helicase Domain Represses Transcriptionmentioning

confidence: 99%

Single cell analysis of Daxx and ATRX-dependent transcriptional repression

Newhart¹,

Rafalska-Metcalf²,

Yang³

et al. 2012

Journal of Cell Science

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SummaryHistone H3.3 is a constitutively expressed H3 variant implicated in the epigenetic inheritance of chromatin structures. Recently, the PML-nuclear body (PML-NB)/Nuclear Domain 10 (ND10) proteins, Daxx and ATRX, were found to regulate replication-independent histone H3.3 chromatin assembly at telomeres and pericentric heterochromatin. As it is not completely understood how PML-NBs/ ND10s regulate transcription and resistance to viral infection, we have used a CMV-promoter-regulated inducible transgene array, at which Daxx and ATRX are enriched, to delineate the mechanisms through which they regulate transcription. When integrated into HeLa cells, which express both Daxx and ATRX, the array is refractory to activation. However, transcription can be induced when ICP0, the HSV-1 E3 ubiquitin ligase required to reverse latency, is expressed. As ATRX and Daxx are depleted from the activated array in ICP0-expressing HeLa cells, this suggests that they are required to maintain a repressed chromatin environment. As histone H3.3 is strongly recruited to the ICP0-activated array but does not co-localize with the DNA, this also suggests that chromatin assembly is blocked during activation. The conclusion that the Daxx and ATRX pathway is required for transcriptional repression and chromatin assembly at this site is further supported by the finding that an array integrated into the ATRX-negative U2OS cell line can be robustly activated and that histone H3.3 is similarly recruited and unincorporated into the chromatin. Therefore, this study has important implications for understanding gene silencing, viral latency and PML-NB/ND10 function.

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“…All CG8290 isoforms share a common N-terminal ADD domain (amino acids . The ADD domain has been reported to confer binding to histone tails and is present in the well-studied mammalian proteins ATRX and DNMT3a (Dhayalan et al 2011;Eustermann et al 2011;Iwase et al 2011). Recently, it was shown that in the context of human ATRX, the ADD domain binds the histone H3 tail, specifically the H3K4me0K9me2/3 modification.…”

Section: Cg8290 Exhibits Affinity For H3k9me2/3 Through An Atrx-like mentioning

confidence: 99%

Heterochromatin-associated interactions of Drosophila HP1a with dADD1, HIPP1, and repetitive RNAs

et al. 2014

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Heterochromatin protein 1 (HP1a) has conserved roles in gene silencing and heterochromatin and is also implicated in transcription, DNA replication, and repair. Here we identify chromatin-associated protein and RNA interactions of HP1a by BioTAP-XL mass spectrometry and sequencing from Drosophila S2 cells, embryos, larvae, and adults. Our results reveal an extensive list of known and novel HP1a-interacting proteins, of which we selected three for validation. A strong novel interactor, dADD1 (Drosophila ADD1) (CG8290), is highly enriched in heterochromatin, harbors an ADD domain similar to human ATRX, displays selective binding to H3K9me2 and H3K9me3, and is a classic genetic suppressor of position-effect variegation. Unexpectedly, a second hit, HIPP1 (HP1 and insulator partner protein-1) (CG3680), is strongly connected to CP190-related complexes localized at putative insulator sequences throughout the genome in addition to its colocalization with HP1a in heterochromatin. A third interactor, the histone methyltransferase MES-4, is also enriched in heterochromatin. In addition to these protein-protein interactions, we found that HP1a selectively associated with a broad set of RNAs transcribed from repetitive regions. We propose that this rich network of previously undiscovered interactions will define how HP1a complexes perform their diverse functions in cells and developing organisms.

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Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin

Cited by 41 publications

References 0 publications

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Single cell analysis of Daxx and ATRX-dependent transcriptional repression

Heterochromatin-associated interactions of Drosophila HP1a with dADD1, HIPP1, and repetitive RNAs

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