Transcriptional adaptor ADA3 of Drosophila melanogaster is required for histone modification, position effect variegation, and transcription
Transcriptional adaptor ADA3 of Drosophila melanogaster is required for histone modification, position effect variegation, and transcription
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DOI：
10.1128/mcb.01307-07
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发表时间：
2008-01-01
影响因子：
5.3
通讯作者：
Ferrus, Alberto
中科院分区：
文献类型：
--
作者：
Grau, Benjamin;Popescu, Cristina;Ferrus, Alberto
黑腹果蝇基因盘（也称为dik或dAda3）编码一种与人类ADA 3有29%相同的蛋白质，ADA 3是含GCN 5的组蛋白乙酰转移酶（HAT）复合物的亚基。果蝇dADA 3是卵子发生的主要贡献者，也是体细胞活力所需的。dADA 3定位于染色体，并且在dGcn 5和dAda2a中显著减少，但在dAda2b突变体背景中不显著减少。在dAda3突变体中，组蛋白H3 K9和K14处的乙酰化显著降低，但K18没有，组蛋白H4 K12处的乙酰化显著降低，但K5、K8和K16没有。此外，H3 S10的磷酸化在dAda3和dGcn5突变体中减少。由X染色体异染色质重排引起的白色（w（m4））和盾形（Hw（v））基因的杂色以dAda3（+）基因剂量依赖性方式被修饰。在涉及Y异染色质（bw（D））、常染色质（Scutoid）的重排或染色体配对的transvection效应（白色和zeste相互作用）中未观察到该效应。scute基因增强子的活性，易洛魁转录因子的目标，在dAda3突变体中被废除。此外，易洛魁族相关表型对dAda3（+）基因剂量敏感。我们得出结论，dADA 3在HAT复合物中起作用，该复合物使H3和H4在特定残基处乙酰化。反过来，这种乙酰化导致特定基因的某些重排和转录的染色质结构效应。
The Drosophila melanogaster gene diskette (also known as dik or dAda3) encodes a protein 29% identical to human ADA3, a subunit of GCN5-containing histone acetyltransferase (HAT) complexes. The fly dADA3 is a major contributor to oogenesis, and it is also required for somatic cell viability. dADA3 localizes to chromosomes, and it is significantly reduced in dGcn5 and dAda2a, but not in dAda2b, mutant backgrounds. In dAda3 mutants, acetylation at histone H3 K9 and K14, but not K18, and at histone H4 K12, but not K5, K8, and K16, is significantly reduced. Also, phosphorylation at H3 S10 is reduced in dAda3 and dGcn5 mutants. Variegation for white (w(m4)) and scute (Hw(v)) genes, caused by rearrangements of X chromosome heterochromatin, is modified in a dAda3(+) gene-dosage-dependent manner. The effect is not observed with rearrangements involving Y heterochromatin (bw(D)), euchromatin (Scutoid), or transvection effects on chromosomal pairing (white and zeste interaction). Activity of scute gene enhancers, targets for Iroquoi transcription factors, is abolished in dAda3 mutants. Also, Iroquoi-associated phenotypes are sensitive to dAda3(+) gene dosage. We conclude that dADA3 plays a role in HAT complexes which acetylate H3 and H4 at specific residues. In turn, this acetylation results in chromatin structure effects of certain rearrangements and transcription of specific genes.