Histone H4 acetylation in <i>Drosophila</i> Frequency of acetylation at different sites defined by immunolabelling with site‐specific antibodies

Munks, R. J. L.; Moore, J J; O’Neill, Laura P.; Turner, Bryan M.

doi:10.1016/0014-5793(91)80695-y

Cited by 77 publications

(28 citation statements)

References 13 publications

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“…In mammals, lysine 16 is clearly the most abundant acetylation site on histone H4 (32,53,55). In bulk chromatin preparations, nearly all acetylated histone H4 molecules are acetylated at H4K16, be it mono-, di-, tri-, or tetra-acetylated H4 (32,53,55). It will be interesting to study whether localization of hMOF coincides with H4K16 acetylation patterns on promoters and/or coding regions previously documented in mammalian cells.…”

Section: Discussionmentioning

confidence: 87%

“…To our knowledge, this is the first report connecting a mammalian histone acetyltransferase to a specific lysine residue in vivo. In mammals, lysine 16 is clearly the most abundant acetylation site on histone H4 (32,53,55). In bulk chromatin preparations, nearly all acetylated histone H4 molecules are acetylated at H4K16, be it mono-, di-, tri-, or tetra-acetylated H4 (32,53,55).…”

Section: Discussionmentioning

confidence: 99%

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hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells

Taipale

Rea

Richter

et al. 2005

Molecular and Cellular Biology

278

289

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Reversible histone acetylation plays an important role in regulation of chromatin structure and function. Here, we report that the human orthologue of Drosophila melanogaster MOF, hMOF, is a histone H4 lysine K16-specific acetyltransferase. hMOF is also required for this modification in mammalian cells. Knockdown of hMOF in HeLa and HepG2 cells causes a dramatic reduction of histone H4K16 acetylation as detected by Western blot analysis and mass spectrometric analysis of endogenous histones. We also provide evidence that, similar to the Drosophila dosage compensation system, hMOF and hMSL3 form a complex in mammalian cells. hMOF and hMSL3 small interfering RNA-treated cells also show dramatic nuclear morphological deformations, depicted by a polylobulated nuclear phenotype. Reduction of hMOF protein levels by RNA interference in HeLa cells also leads to accumulation of cells in the G 2 and M phases of the cell cycle. Treatment with specific inhibitors of the DNA damage response pathway reverts the cell cycle arrest caused by a reduction in hMOF protein levels. Furthermore, hMOF-depleted cells show an increased number of phospho-ATM and ␥H2AX foci and have an impaired repair response to ionizing radiation. Taken together, our data show that hMOF is required for histone H4 lysine 16 acetylation in mammalian cells and suggest that hMOF has a role in DNA damage response during cell cycle progression.Nucleosomes composed of DNA and histones define the fundamental structural unit of chromatin, which acts as a scaffold for nuclear processes such as transcription and replication. By modifying the nucleosomal structure in several ways, the chromatinized DNA can be made either more or less accessible. Alterations to chromatin structure are usually brought about in three different ways: by ATP-dependent remodeling of nucleosomes, by replacement of standard histones with histone variants, and by covalently modifying the N-terminal tails of histones. Histone modifications include acetylation, phosphorylation, methylation, ubiquitination, sumoylation, and poly(ADP-ribosyl)ation (for a review, see reference 54). Histone acetylation is the best-characterized modification and is controlled by histone acetyltransferases (HATs) and histone deacetylases.Sequence analysis of HAT proteins reveal that they can be classified in distinct families, with each family having a characteristic substrate specificity (12). GNAT (GCN5-related Nacetyltransferases) family members mainly acetylate lysines on the histone H3 tail. The founding members of the other family, MYST, include Saccharomyces cerevisiae Ybf2p/Sas3p and Sas2p and human MOZ and Tip60 (56). The MYST homology domain is exceptionally well conserved among all family members. This region includes the acetyl coenzyme A binding domain similar to the one found in GNAT acetyltransferases (41) as well as a C 2 HC-type zinc finger. Recently, the crystal structure of Esa1, an essential yeast HAT, showed that even though the MYST and GNAT family share sequence homology only in motif A, there...

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells

Taipale

Rea

Richter

et al. 2005

Molecular and Cellular Biology

278

289

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“…Site-specific histone acetylation in Sciara chromatin Histone acetylation sites show a high degree of evolutionary conservation, but important differences are known to exist in the control of histone H4 acetylation in different species (for a review, see Munks et al, 1991;Strahl and Allis, 2000). From our results, in Sciara germ cells chromatin, from the four possible acetylable lysine residues of histone H4 (Lys16, Lys12, Lys8 and Lys5), sites 8 and 12 are predominantly acetylated, in contrast to sites 5 and 16.…”

Section: Discussionmentioning

confidence: 99%

Differential acetylation of histones H3 and H4 in paternal and maternal germline chromosomes during development of sciarid flies

Goday

Ruiz

2002

Journal of Cell Science

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A classic example of chromosome elimination and genomic imprinting is found in sciarid flies (Diptera. Sciaridae), where whole chromosomes of exclusively paternal origin are discarded from the genome at different developmental stages. Two types of chromosome elimination event occur in the germline. In embryos of both sexes, the extrusion of a single paternal X chromosome occurs in early germ nuclei and in male meiotic cells the whole paternal complement is discarded. In sciarids, early germ nuclei remain undivided for a long time and exhibit a high degree of chromatin compaction,so that chromosomes are cytologically individualized. We investigated chromatin differences between parental chromosomes in Sciara ocellaris and S. coprophila by analyzing histone acetylation modifications in early germ nuclei. We examined germ nuclei from early embryonic stages to premeiotic larval stages, male meiotic cell and early somatic nuclei following fertilization. In early germ cells, only half of the regular chromosome complement is highly acetylated for histones H4 and H3. The chromosomes that are highly acetylated are paternally derived. An exception is the paternal X chromosome that is eliminated from germ nuclei. At later stages preceding the initiation of mitotic gonial divisions, all chromosomes of the germline complement show similar high levels of histone H4/H3 acetylation. In male meiosis, maternal chromosomes are highly acetylated for histones H4 and H3, whereas the entire paternal chromosome set undergoing elimination appears under-acetylated. The results suggest that histone acetylation contributes towards specifying the imprinted behavior of germline chromosomes in sciarids.

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“…However, this is not the case in Drosophila cells. In both the Kc and SL2 cultured cell lines, treatment with either butyrate or TSA leads to accumulation of acetylated H4 isoforms that is always significantly less than in mammalian cells treated in the same way [48]. Irrespective of the length of exposure to the inhibitors or their concentration, the level of acetylation never reached a stage at which the most acetylated isoforms (i.e.…”

Section: Evidence For Regionally Localized Lysine-specific Acetyltramentioning

confidence: 97%

Histone acetylation as an epigenetic determinant of long-term transcriptional competence

Turner¹

1998

Cellular and Molecular Life Sciences (CMLS)

195

114

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All four histones of the nucleosome core particle are subject to post-translational acetylation of selected lysine residues in their amino-terminal domains. The modification is ubiquitous and frequent. Steady-state levels of acetylation have been shown to vary from one part of the genome to another and to be maintained by a dynamic balance between the activities of two enzyme families, the histone acetyltransferases (HATs) and deacetylases (HDAs). The recent demonstration that some at least of these enzymes are homologous to, or identical with, known regulators of transcription, has renewed interest in the involvement of histone acetylation in transcriptional control. Acetylation might influence the initiation and/or elongation phases of transcription in a chromatin context, possibly by regulating the accessibility of nucleosomal DNA to transcription factors or the displacement of histones by the progressing transcription complex. But there is also evidence to suggest that acetylation might be involved in the longer-term regulation of transcription, acting as a marker by which states of genetic activity or inactivity are maintained from one cell generation to the next. This review outlines the evidence for such a role, using centric heterochromatin and the dosage-compensated male X chromosome in Drosophila as model systems, and suggests possible mechanisms by which it might operate.

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Histone H4 acetylation in Drosophila Frequency of acetylation at different sites defined by immunolabelling with site‐specific antibodies

Cited by 77 publications

References 13 publications

hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells

hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells

Differential acetylation of histones H3 and H4 in paternal and maternal germline chromosomes during development of sciarid flies

Histone acetylation as an epigenetic determinant of long-term transcriptional competence

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