Functional consequences of histone modifications

Iizuka, Masaru; Smith, M. Mitchell

doi:10.1016/s0959-437x(03)00020-0

Cited by 273 publications

(186 citation statements)

References 63 publications

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“…These PTMs determine open and closed chromatin conformations, which, in turn, regulate the differential access and recruitment of transcription factors and other regulatory chromatin-binding proteins to DNA. [3][4][5] Among these histone modifications, histone acetylation is the most well-studied modification, which occurs at the ε-amino groups of evolutionarily conserved lysine residues located at the N termini. Although all core histones are acetylated in vivo, modifications of histones H3 and H4 are more extensively characterized than those of H2A and H2B.…”

Section: Open Questionsmentioning

confidence: 99%

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Schultz

2016

Cell Death Differ

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Oocyte and preimplantation embryo development entail dynamic changes in chromatin structure and gene expression, which are regulated by a number of maternal and zygotic epigenetic factors. Histone deacetylases (HDACs), which tighten chromatin structure, repress transcription and gene expression by removing acetyl groups from histone or non-histone proteins. HDAC1 and HDAC2 are two highly homologous Class I HDACs and display compensatory or specific roles in different cell types or in response to different stimuli and signaling pathways. We summarize here the current knowledge about the functions of HDAC1 and HDAC2 in regulating histone modifications, transcription, DNA methylation, chromosome segregation, and cell cycle during oocyte and preimplantation embryo development. What emerges from these studies is that although HDAC1 and HDAC2 are highly homologous, HDAC2 is more critical than HDAC1 for oocyte development and reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. In eukaryotes, DNA is organized into a highly ordered nucleoprotein assembly called chromatin, whose fundamental unit is the nucleosome. The nucleosome consists of 146 bp of DNA wrapped around a histone core comprised of two molecules each of histones H2A, H2B, H3 and H4. Histone H1 is bound to linker DNA between nucleosomes. 1,2 Histones are subject to multiple post-translational modifications (PTMs), including acetylation, methylation, ubiquitylation, phosphorylation, and sumoylation. These PTMs determine open and closed chromatin conformations, which, in turn, regulate the differential access and recruitment of transcription factors and other regulatory chromatin-binding proteins to DNA. 3-5 Among these histone modifications, histone acetylation is the most well-studied modification, which occurs at the ε-amino groups of evolutionarily conserved lysine residues located at the N termini. Although all core histones are acetylated in vivo, modifications of histones H3 and H4 are more extensively characterized than those of H2A and H2B. Abbreviations: HDAC, histone deacetylase; HAT, histone acetyl transferase; PTM, post-translational modification; KDAC, lysine deacetylase; TSA, trichostatin A; NAD + , nicotinamide adenine dinucleotide; HAD, HDAC association domain ; GVBD, germinal vesicle breakdown; ChIP-seq, chromatin immunoprecipitation sequencing; TFIID, transcription factor II D; YY1, yin yang 1; Pol II CTD S2, serine 2 within the RNApolymerase II C-terminal domain; H3K4, lysine 4 of histone 3; H3K9, lysine 9 of histone 3; H4K16, lysine 16 of histone 4; SIRT, NAD-dependent deacetylase sirtuin; TBP2, TATA-binding protein 2; DNMT, DNA methyltransferases; RBAP46, retinoblastoma binding protein P46; RNAi, RNA interference; aa, amino acidic; BrUTP, 5-Bromouridine 5′-triphosphate; qRT-PCR, quantitative reverse transcription polymerase chain reaction;

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Section: Open Questionsmentioning

confidence: 99%

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Schultz

2016

Cell Death Differ

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“…Histone modifications such as phosphorylation, methylation, acetylation, and deacetylation provide a mechanism by which chromatin structure is modulated to affect gene expression both positively and negatively (for reviews see Strahl and Allis, 2000;Iizuka and Smith, 2003;Kurdistani and Grunstein, 2003). The acetylation of lysine residues on histone N-terminal tails is classically linked to increases in gene expression and more directly to roles in transcriptional activation.…”

Section: Introductionmentioning

confidence: 99%

“…By contrast, deacetylation of histones is most frequently correlated with transcriptionally silent chromatin. As more is learned about the enzymes catalyzing these modifications, the histone acetyltransferases (HATs) and histone deacetylases (HDACs), simple functional distinctions between acetylation and deacetylation of histones do not hold (Iizuka and Smith, 2003). For example, in several organisms, mutations in RPD3, a gene encoding a deacetylase, lead to increases in silencing rather than the expected decreases (DeRubertis et al, 1996;Rundlett et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Clarke

Samal

Pillus

2006

MBoC

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Among acetyltransferases, the MYST family enzyme Esa1p is distinguished for its essential function and contribution to transcriptional activation and DNA double-stranded break repair. Here we report that Esa1p also plays a key role in silencing RNA polymerase II (Pol II)-transcribed genes at telomeres and within the ribosomal DNA (rDNA) of the nucleolus. These effects are mediated through Esa1p's HAT activity and correlate with changes within the nucleolus. Esa1p is enriched within the rDNA, as is the NAD-dependent protein deacetylase Sir2p, and the acetylation levels of key Esa1p histone targets are reduced in the rDNA in esa1 mutants. Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA recombination, esa1 effects are more modest yet result in distinct structural changes of rDNA chromatin. Surprisingly, increased expression of ESA1 can bypass the requirement for Sir2p in rDNA silencing, suggesting that these two enzymes with seemingly opposing activities both contribute to achieve optimal nucleolar chromatin structure and function. INTRODUCTIONHistone modifications such as phosphorylation, methylation, acetylation, and deacetylation provide a mechanism by which chromatin structure is modulated to affect gene expression both positively and negatively (for reviews see Strahl and Allis, 2000;Iizuka and Smith, 2003;Kurdistani and Grunstein, 2003). The acetylation of lysine residues on histone N-terminal tails is classically linked to increases in gene expression and more directly to roles in transcriptional activation. By contrast, deacetylation of histones is most frequently correlated with transcriptionally silent chromatin. As more is learned about the enzymes catalyzing these modifications, the histone acetyltransferases (HATs) and histone deacetylases (HDACs), simple functional distinctions between acetylation and deacetylation of histones do not hold (Iizuka and Smith, 2003). For example, in several organisms, mutations in RPD3, a gene encoding a deacetylase, lead to increases in silencing rather than the expected decreases (DeRubertis et al., 1996;Rundlett et al., 1996). This brings forward the possibility that histone acetylation may play an important part in both silent and active chromatin. In addition, coactivator proteins, such as the histone acetyltransferases p300 and CBP and nuclear hormone receptors, appear to have roles in transcriptional repression through acetylation and association with particular binding partners (for examples, see Chen and Li, 1998;Waltzer and Bienz, 1998;Baluchamy et al., 2003;Girdwood et al., 2003;Rajabi et al., 2005). Thus, understanding of multiple roles for acetylation in controlling gene expression is expanding.In Saccharomyces cerevisiae, there are three regions of the genome controlled by chromatin-mediated transcriptional silencing: telomeres, the silent mating-type loci HMR and HML, and the rDNA array. Many factors are important for transcriptional silencing at subsets of these loci including the four core histones, the repressor activator protein Rap1...

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“…25 These modifications are reported to affect chromosome function via two distinct mechanisms. 26 Nearly all modifications alter the electrostatic charge of histones, which could change the structural properties of histones or their binding to the DNA. On the other hand, modifications could create binding surfaces for protein recognition modules, and thus recruit specific functional complexes to their appropriate sites of action.…”

Section: Epigeneticsmentioning

confidence: 99%

“…24,28 There is sufficient evidence to show that increased levels of histone acetylation are highly correlated with increased transcriptional activity, whereas decreased levels of acetylation will lead to repression of gene expression. 25,29 The acetylation and deacetylation of histones are dynamic processes that depend on the balance between histone acetyltransferases and HDACs. 28,30 Histone acetyltransferases can transfer the acetyl moiety from acetyl coenzyme A onto the lysine residues of histone proteins, whereas HDACs usually repress transcription.…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetic regulation of pulmonary arterial hypertension

Cheng

2011

Hypertens Res

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Pulmonary arterial hypertension (PAH) is diagnosed as a sustained elevation of pulmonary arterial pressure to more than 25 mm Hg at rest or to more than 30 mm Hg with exercise. PAH is an intrinsic disease of the pulmonary vascular smooth muscle and endothelial cells in association with plexiform lesions, medial thickening, concentric laminar intimal fibrosis and thrombotic lesions. Pulmonary vascular remodeling is the characteristic pathological change of PAH. The pathogenesis of PAH has been studied at the level of smooth muscle and endothelial cells. Existing research does not adequately explain susceptibility to the disease, and recent evidence reveals that epigenetic alterations may be involved in PAH. Epigenetics refers to all heritable changes in phenotype or in gene expression states, including chromatin remodeling, DNA methylation, histone modification and RNA interference, which are not involved in the DNA sequence itself. This review will focus on recent advances in epigenetics related to PAH, including epigenetic changes of superoxide dismutase, endothelial nitric oxide synthase and the bone morphogenetic protein signaling pathway. This will provide new insight for improved treatment and prevention of PAH. Future work aimed at specific epigenetic treatments may prove to be an effective therapy for patients with PAH.

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Functional consequences of histone modifications

Cited by 273 publications

References 63 publications

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Epigenetic regulation of pulmonary arterial hypertension

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