Journal ArticleDOI
Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes.
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TLDR
The higher resolution afforded by “stretching” the centromeric heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4 acetylation in these domains, and considers the implications of these observations in relation to chromatin conformation and activity.Abstract:
Unfixed metaphase chromosome preparations from human lymphocyte cultures were immunofluorescently labelled using antibodies to defined histone epitopes. Both mouse monoclonal antibody HBC-7, raised against the N-terminal region of H2B, and rabbit serum R5/12, which recognizes H4 acetylated at Lys-12, gave non-uniform labelling patterns, whereas control antibodies against total histone fractions H4 and H1 produced homogeneous fluorescence. HBC-7 bound approximately uniformly to the bulk of the chromosomes, but the major heterochromatic domains of chromosomes 1, 9, 15, 16 and the Y showed significantly brighter fluorescence. Serum R5/12 indicated an overall reduction in acetylation of H4 in metaphase chromosomes compared with interphase nuclei, although some specific chromosomal locations had considerably elevated acetylation levels. Acetylation levels in the major heterochromatic domains appeared extremely low. To investigate further the differences noted in heterochromatin labelling, metaphases from cultures grown in the presence of various agents known to induce undercondensation of the major heterochromatic domains were similarly immunolabelled. Decondensed heterochromatin no longer exhibited higher than normal immunofluorescence levels with HBC-7. The higher resolution afforded by "stretching" the centromeric heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4 acetylation in these domains. We consider the implications of these observations in relation to chromatin conformation and activity.read more
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Journal ArticleDOI
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
TL;DR: It is shown that ATM is held inactive in unirradiated cells as a dimer or higher-order multimer, with the kinase domain bound to a region surrounding serine 1981 that is contained within the previously described ‘FAT’ domain.
Journal ArticleDOI
Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.
Antoine H.F.M. Peters,Dónal O'Carroll,Harry Scherthan,Karl Mechtler,Stephan Sauer,Christian Schöfer,Klara Weipoltshammer,Michaela Pagani,Monika Lachner,Alexander Kohlmaier,Susanne Opravil,Michael P. Doyle,Maria Sibilia,Thomas Jenuwein +13 more
TL;DR: In vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.
Journal ArticleDOI
Purification, sequence, and cellular localization of a novel chromosomal protein that binds to Methylated DNA
Joe D. Lewis,Joe D. Lewis,Richard R. Meehan,Richard R. Meehan,William J. Henzel,Ingrid Maurer-Fogy,Peter Jeppesen,Franz Klein,Adrian Bird,Adrian Bird +9 more
TL;DR: This work reports the identification, purification, and cDNA cloning of a novel MeCP called MeCP2, which unlike MeCP1, the new protein is able to bind to DNA that contains a single methyl-CpG pair.
Journal ArticleDOI
The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression
Peter Jeppesen,Bryan M. Turner +1 more
TL;DR: In this paper, immunolabeled human and mouse metaphase chromosomes with antibodies specific for the acetylated isoforms of histone H4 were labeled in regions corresponding to conventional R bands (regions enriched in coding DNA), except for a single chromosome in female cells.
Journal ArticleDOI
Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component.
Christèle Maison,Delphine Bailly,Antoine H.F.M. Peters,Jean-Pierre Quivy,Danièle Roche,Angela Taddei,Angela Taddei,Monika Lachner,Thomas Jenuwein,Geneviève Almouzni +9 more
TL;DR: The results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin, and identify an RNA- and histone modification–dependent structure that brings methylated H1 protein–binding tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.
References
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Journal ArticleDOI
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