Hira-Dependent Histone H3.3 Deposition Facilitates PRC2 Recruitment at Developmental Loci in ES Cells

Banaszynski, Laura A.; Wen, Duancheng; Dewell, Scott; Whitcomb, Sarah J.; Lin, Mingyan; Diaz, Nichole; Elsässer, Simon J.; Chapgier, Ariane; Goldberg, Aaron D; Canaani, Eli; Rafii, Shahin; Zheng, Deyou; Allis, C. David

doi:10.1016/j.cell.2013.08.061

Cited by 249 publications

(377 citation statements)

References 47 publications

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“…Therefore, these results support a model whereby OGT binds and modifies HIRA and promotes HIRA-mediated nucleosome assembly of H3.3-H4 and cellular senescence. Histone variant H3.3 is assembled into nucleosomes at distinct chromatin domains in a replication-independent process (11)(12)(13)(14)(15)(16)(17)(18). In addition, histone H3.3 is mutated in high-grade pediatric brain tumors, chondroblastoma, and giant cell tumors (56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, along with H4, canonical histone H3.1/H3.2 is deposited by the histone chaperone CAF-1 during S phase, whereas H3.3 is assembled into nucleosomes at pericentric and telomeric regions by DAXX/ATRX, and at genic regions by the HIRA complex (11)(12)(13)(14)(15)(16)(17)(18). In addition to histone chaperones, posttranslational modifications on newly synthesized histones impact nucleosome assembly, in part by regulating the interactions between histone chaperones and their histone cargo.…”

mentioning

confidence: 99%

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O-linked N -acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence

Lee

Zhang

2016

Proc. Natl. Acad. Sci. U.S.A.

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The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

O-linked N -acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence

Lee

Zhang

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…It is thus enriched in areas of increased nucleosome turnover including transcribed genes but is also found in silent regions including pericentromeric heterochromatin and telomeres (Szenker et al , 2011). H3.3 is essential for development as it is necessary for proper trimethylation of H3K27 at genes regulated by the polycomb‐repressive complex 2 (Banaszynski et al , 2013). Complete absence of H3.3 in mice thus results in peri‐implantation lethality (Jang et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

et al. 2016

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Immunoglobulin diversification is driven by activation‐induced deaminase (AID), which converts cytidine to uracil within the Ig variable (IgV) regions. Central to the recruitment of AID to the IgV genes are factors that regulate the generation of single‐stranded DNA (ssDNA), the enzymatic substrate of AID. Here, we report that chicken DT40 cells lacking variant histone H3.3 exhibit reduced IgV sequence diversification. We show that this results from impairment of the ability of AID to access the IgV genes due to reduced formation of ssDNA during IgV transcription. Loss of H3.3 also diminishes IgV R‐loop formation. However, reducing IgV R‐loops by RNase HI overexpression in wild‐type cells does not affect IgV diversification, showing that these structures are not necessary intermediates for AID access. Importantly, the reduction in the formation of AID‐accessible ssDNA in cells lacking H3.3 is independent of any effect on the level of transcription or the kinetics of RNAPII elongation, suggesting the presence of H3.3 in the nucleosomes of the IgV genes increases the chances of the IgV DNA becoming single‐stranded, thereby creating an effective AID substrate.

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“…This result indicates that maternal H3.3 is specifically involved in the reactivation of gene expression in SCNT embryos during reprogramming and may not be required for the maintenance of gene expression, consistent with our observation of the maintenance of self-renewal in H3.3KD ESCs. 34 RNA-seq confirmed that many key pluripotency genes (e.g., Oct4, Nanog) fail to become activated upon SCNT in the absence of H3.3.…”

Section: Reactivation Of Pluripotencyassociated Genes Is Dependent Upmentioning

confidence: 94%

H3.3 replacement facilitates epigenetic reprogramming of donor nuclei in somatic cell nuclear transfer embryos

Wen

Banaszynski

Rosenwaks

et al. 2014

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T ransfer of a somatic nucleus into an enucleated oocyte is the most efficient approach for somatic cell reprogramming. While this process is known to involve extensive chromatin remodeling of the donor nucleus, the maternal factors responsible and the underlying chromatin-based mechanisms remain largely unknown. Here we discuss our recent findings demonstrating that the histone variant H3.3 plays an essential role in reprogramming and is required for reactivation of key pluripotency genes in somatic cell nuclear transfer (SCNT) embryos. Maternal-derived H3.3 replaces H3 in the donor nucleus shortly after oocyte activation, with the amount of replacement directly related to the differentiation status of the donor nucleus in SCNT embryos. We provide additional evidence to suggest that de novo synthesized H3.3 replaces histone H3 carrying repressive modifications in the donor nuclei of SCNT embryos, and hypothesize that replacement may occur at specific loci that must be reprogrammed for gene reactivation.

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Hira-Dependent Histone H3.3 Deposition Facilitates PRC2 Recruitment at Developmental Loci in ES Cells

Cited by 249 publications

References 47 publications

O-linked N -acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence

O-linked N -acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

H3.3 replacement facilitates epigenetic reprogramming of donor nuclei in somatic cell nuclear transfer embryos

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