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HP1 proteins are essential for a dynamic nuclear response that rescues the function of perturbed heterochromatin in primary human cells
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Zhang R Liu ST Chen W Bonner M Pehrson J Yen TJ Adams PD 《Molecular and cellular biology》2007,27(3):949-962
Cellular information is encoded genetically in the DNA nucleotide sequence and epigenetically by the "histone code," DNA methylation, and higher-order packaging of DNA into chromatin. Cells possess intricate mechanisms to sense and repair damage to DNA and the genetic code. However, nothing is known of the mechanisms, if any, that repair and/or compensate for damage to epigenetically encoded information, predicted to result from perturbation of DNA and histone modifications or other changes in chromatin structure. Here we show that primary human cells respond to a variety of small molecules that perturb DNA and histone modifications by recruiting HP1 proteins to sites of altered pericentromeric heterochromatin. This response is essential to maintain the HP1-binding kinetochore protein hMis12 at kinetochores and to suppress catastrophic mitotic defects. Recruitment of HP1 proteins to pericentromeres depends on histone H3.3 variant deposition, mediated by the HIRA histone chaperone. These data indicate that defects in pericentromeric epigenetic heterochromatin modifications initiate a dynamic HP1-dependent response that rescues pericentromeric heterochromatin function and is essential for viable progression through mitosis. 相似文献
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What histone code for DNA repair? 总被引:8,自引:0,他引:8
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Defining an epigenetic code 总被引:1,自引:0,他引:1
Turner BM 《Nature cell biology》2007,9(1):2-6
The nucleosome surface is decorated with an array of enzyme-catalysed modifications on histone tails. These modifications have well-defined roles in a variety of ongoing chromatin functions, often by acting as receptors for non-histone proteins, but their longer-term effects are less clear. Here, an attempt is made to define how histone modifications operate as part of a predictive and heritable epigenetic code that specifies patterns of gene expression through differentiation and development. 相似文献
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Histone acetylation and an epigenetic code 总被引:62,自引:0,他引:62
Turner BM 《BioEssays : news and reviews in molecular, cellular and developmental biology》2000,22(9):836-845
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Nikolov M Stützer A Mosch K Krasauskas A Soeroes S Stark H Urlaub H Fischle W 《Molecular & cellular proteomics : MCP》2011,10(11):M110.005371
DNA and histone modifications direct the functional state of chromatin and thereby the readout of the genome. Candidate approaches and histone peptide affinity purification experiments have identified several proteins that bind to chromatin marks. However, the complement of factors that is recruited by individual and combinations of DNA and histone modifications has not yet been defined. Here, we present a strategy based on recombinant, uniformly modified chromatin templates used in affinity purification experiments in conjunction with SILAC-based quantitative mass spectrometry for this purpose. On the prototypic H3K4me3 and H3K9me3 histone modification marks we compare our method with a histone N-terminal peptide affinity purification approach. Our analysis shows that only some factors associate with both, chromatin and peptide matrices but that a surprisingly large number of proteins differ in their association with these templates. Global analysis of the proteins identified implies specific domains mediating recruitment to the chromatin marks. Our proof-of-principle studies show that chromatin templates with defined modification patterns can be used to decipher how the histone code is read and translated. 相似文献
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