Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histone variant H3.3 marks active chromatin by replacing the conventional histone H3.1. In this study, we investigate the detailed mechanism of H3.3 replication-independent deposition. We found that the death domain-associated protein DAXX and the chromatin remodeling factor ATRX (alpha-thalassemia/mental retardation syndrome protein) are specifically associated with the H3.3 deposition machinery. Bacterially expressed DAXX has a marked binding preference for H3.3 and assists the deposition of (H3.3-H4)(2) tetramers on naked DNA, thus showing that DAXX is a H3.3 histone chaperone. In DAXX-depleted cells, a fraction of H3.3 was found associated with the replication-dependent machinery of deposition, suggesting that cells adapt to the depletion. The reintroduced DAXX in these cells colocalizes with H3.3 into the promyelocytic leukemia protein (PML) bodies. Moreover, DAXX associates with pericentric DNA repeats, and modulates the transcription from these repeats through assembly of H3.3 nucleosomes. These findings establish a new link between the PML bodies and the regulation of pericentric DNA repeat chromatin structure. Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3.
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PMID:The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. 2059 28

The histone variant H3.3 and the canonical histone H3.1, which differ in only 4- to 5-aa positions, are coexpressed in complex multicellular eukaryotes from fly to human and plant. H3.3 is mainly associated with active chromatin by replacing H3.1 through chaperones such as histone regulator A, death domain associated protein DAXX, thalassemia/mental retardation syndrome X-linked homolog ATRX, or proto-oncogene protein DEK and plays important roles in the germline, epigenetic memory, and reprogramming. However, the signals within H3.3 that serve as a guide for its dynamic deposition or depletion in plant chromatin are not clear. Here, we show that Arabidopsis histone H3.3 differs from H3.1 by 4-aa sites: amino acids 31, 41, 87, and 90. Although histone H3.1 is highly enriched in chromocenters, H3.3 is present in nucleolar foci in addition to being diffusely distributed in the nucleoplasm. We have evaluated the function of the 4 aa that differ between H3.1 and H3.3. We show that amino acid residue 87, and to some extent residue 90, of Arabidopsis histone H3.3 are critical for its deposition into rDNA arrays. When RNA polymerase I-directed nucleolar transcription is inhibited, wild type H3.3, but not H3.3 containing mutations at residues 31 and 41, is depleted from the rDNA arrays. Together, our results are consistent with a model in which amino acids 87 and 90 in the core domain of H3.3 guide nucleosome assembly, whereas amino acids 31 and 41 in the N-terminal tail of Arabidopsis H3.3 guide nucleosome disassembly in nucleolar rDNA.
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PMID:Four amino acids guide the assembly or disassembly of Arabidopsis histone H3.3-containing nucleosomes. 2167 Mar 3