Modulation of ISWI function by site-specific histone acetylation
Modulation of ISWI function by site-specific histone acetylation
复制标题
DOI：
10.1093/embo-reports/kvf056
复制
发表时间：
2002-03-01
期刊：
影响因子：
7.7
通讯作者：
Tamkun, JW
中科院分区：
文献类型：
--
作者：
Corona, DFV;Clapier, CR;Tamkun, JW
果蝇ISWI是染色质重塑ATP酶SW 12/SNF 2家族的成员，其突变改变了男性X染色体的整体结构。由于剂量补偿，该染色体上的基因转录相对于雌性增加2倍，这一过程涉及组蛋白H4在赖氨酸16（H4 K16）处的乙酰化。在这里，我们表明，阻断H4 K16乙酰化抑制X染色体缺陷造成的损失ISWI功能的男性。与此相反，在ISWI突变的女性中H4 K16的强制乙酰化导致与在ISWI突变的男性中所见的X染色体缺陷难以区分的X染色体缺陷。MOF（使H4 K16乙酰化的组蛋白乙酰转移酶）的表达增加，强烈增强由ISWI功能的部分丧失引起的表型。肽竞争测定显示，H4 K16乙酰化降低了ISWI与其底物有效相互作用的能力。这些发现表明，H4 K16乙酰化直接抵消染色质压实介导的ISWI ATP酶。
Mutations in Drosophila ISWI, a member of the SW12/SNF2 family of chromatin remodeling ATPases, alter the global architecture of the male X chromosome. The transcription of genes on this chromosome is increased 2-fold relative to females due to dosage compensation, a process involving the acetylation of histone H4 at lysine 16 (H4K16). Here we show that blocking H4K16 acetylation suppresses the X chromosome defects resulting from loss of ISWI function in males. In contrast, the forced acetylation of H4K16 in ISWI mutant females causes X chromosome defects indistinguishable from those seen in ISWI mutant males. Increased expression of MOF, the histone acetyltransferase that acetylates H4K16, strongly enhances phenotypes resulting from the partial loss of ISWI function. Peptide competition assays revealed that H4K16 acetylation reduces the ability of ISWI to interact productively with its substrate. These findings suggest that H4K16 acetylation directly counteracts chromatin compaction mediated by the ISWI ATPase.