30 nm Chromatin Fibre Decompaction Requires both H4-K16 Acetylation and Linker Histone Eviction

Robinson, Philip J.; An, Woojin; Routh, Andrew; Martino, Fabrizio; Chapman, Lynda; Roeder, Robert G.; Rhodes, Daniela

doi:10.1016/j.jmb.2008.04.050

Cited by 292 publications

(320 citation statements)

References 54 publications

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“…During mitosis in yeast, H3S10ph directly recruits the deacetylase Hst2p to reduce the overall H4K16ac levels and to allow chromosome condensation [175•]. This is consistent with other studies that showed that H4K16ac is a key acetylation mark that regulates chromatin compaction [176][177][178][179].…”

Section: Histone Phosphorylationsupporting

confidence: 87%

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

2015

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The eukaryotic genome is highly complex and compartmentalized into distinct physical and functional domains. Although the majority of genomic DNA is wrapped around histone proteins in the same manner to form repeating units of nucleosomes, the use of distinct histone variants and the myriad of posttranslational modifications (PTMs) on different histones and amino acid residues create great diversity among these nucleosomes. In this review, we summarize some of the most recent findings in the histone variant and PTM fields and update the readers on our current understanding of various histone-related pathways. Furthermore, we discuss how homotypic or heterotypic deposition of histone variants as well as symmetric or asymmetric histone PTMs within the nucleosome context can further expand the diversity and functionality of chromatin. Altogether, this review highlights the complexity of chromatin composition and organization and their regulatory functions within the eukaryotic genome.

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Section: Histone Phosphorylationsupporting

confidence: 87%

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

2015

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“…Other studies of in vitro assembled nucleosomal arrays revealed that individual histone N-tails (except the H4 N-tail) play only moderate effects on highorder chromatin structure (30,34). However, by revealing a specific requirement for the H2A or the H3 N-tail, our results raise the intriguing possibility that these tails play a redundant role in maintaining intact cellular chromatin.…”

Section: Double Deletion Of the Histone N-tails Uncovers Unidentifiedmentioning

confidence: 38%

Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast

Kim

Hsu

Smith

et al. 2012

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

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A large body of literature provides compelling evidence for the role of evolutionarily conserved core histone residues in various biological processes. However, site-directed mutagenesis of individual residues that are known to be sites of posttranslational modifications often does not result in clear phenotypic defects. In some cases, the combination of multiple mutations can give rise to stronger phenotypes, implying functional redundancy between distinct residues on histones. Here, we examined the “histone redundancy hypothesis” by characterizing double deletion of all pairwise combinations of amino-terminal tails (N-tails) from the four core histones encoded in budding yeast. First, we found that multiple lysine residues on the N-tails of both H2A and H4 are redundantly involved in cell viability. Second, simultaneous deletion of N-tails from H2A and H3 leads to a severe growth defect, which is correlated with perturbed gross chromatin structure in the mutant cells. Finally, by combining point mutations on H3 with deletion of the H2A N-tail, we revealed a redundant role for lysine 4 on H3 and the H2A N-tail in hydroxyurea-mediated response. Altogether, these data suggest that the N-tails of core histones share previously unrecognized, potentially redundant functions that, in some cases are different from those of the widely accepted H2A/H2B and H3/H4 dimer pairs.

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“…However, it has recently been shown that the HDAC1/metastasis-associated 1 (MTA1) complex (of NuRD) is regulated by a molecule of inositol tetraphosphate [Ins(1,4,5,6)P 4 ] (IP 4 ), which regulates its enzymatic activity, presumably in response to external signaling pathways (5). Because deacetylation of histone tails results in the tightening of nucleosomal arrays (6), the physiological roles of HDAC1/2 have mostly been defined within the context of transcriptional repression. However, genome-wide mapping of HDAC1 target genes reveals a correlation between binding and transcriptional activity (7,8), suggesting that HDAC1/2 may play a role in the cyclical acetylation of histones at active promoters (9).…”

mentioning

confidence: 99%

Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells

Jamaladdin

Kelly

O’Regan

et al. 2014

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

140

125

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Histone deacetylases 1 and 2 (HDAC1/2) form the core catalytic components of corepressor complexes that modulate gene expression. In most cell types, deletion of both Hdac1 and Hdac2 is required to generate a discernible phenotype, suggesting their activity is largely redundant. We have therefore generated an ES cell line in which Hdac1 and Hdac2 can be inactivated simultaneously. Loss of HDAC1/2 resulted in a 60% reduction in total HDAC activity and a loss of cell viability. Cell death is dependent upon cell cycle progression, because differentiated, nonproliferating cells retain their viability. Furthermore, we observe increased mitotic defects, chromatin bridges, and micronuclei, suggesting HDAC1/2 are necessary for accurate chromosome segregation. Consistent with a critical role in the regulation of gene expression, microarray analysis of Hdac1/2-deleted cells reveals 1,708 differentially expressed genes. Significantly for the maintenance of stem cell self-renewal, we detected a reduction in the expression of the pluripotent transcription factors, Oct4, Nanog, Esrrb, and Rex1. HDAC1/2 activity is regulated through binding of an inositol tetraphosphate molecule (IP 4 ) sandwiched between the HDAC and its cognate corepressor. This raises the important question of whether IP 4 regulates the activity of the complex in cells. By rescuing the viability of double-knockout cells, we demonstrate for the first time (to our knowledge) that mutations that abolish IP 4 binding reduce the activity of HDAC1/2 in vivo. Our data indicate that HDAC1/2 have essential and pleiotropic roles in cellular proliferation and regulate stem cell self-renewal by maintaining expression of key pluripotent transcription factors.

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30 nm Chromatin Fibre Decompaction Requires both H4-K16 Acetylation and Linker Histone Eviction

Cited by 292 publications

References 54 publications

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast

Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells

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