Drosophila Transcription Factor Tramtrack69 Binds MEP1 To Recruit the Chromatin Remodeler NuRD
Drosophila Transcription Factor Tramtrack69 Binds MEP1 To Recruit the Chromatin Remodeler NuRD
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DOI：
10.1128/mcb.00266-10
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发表时间：
2010-11-01
影响因子：
5.3
通讯作者：
Verrijzer, C. Peter
中科院分区：
文献类型：
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作者：
Reddy, B. Ashok;Bajpe, Prashanth Kumar;Verrijzer, C. Peter
atp依赖性染色质重塑复合体是染色质结构和基因转录的重要调节因子。重塑者如何以基因选择的方式起作用仍然是个谜。结合果蝇转录因子Tramtrack69 （TTK69）蛋白的酵母双杂交筛选鉴定出MEP1。蛋白质组学表征显示，MEP1是NuRD重塑器紧密相关的亚基，包含Mi2酶核心atp酶。此外，我们鉴定了人类口腔癌中缺失1 （DOC1）的苍蝇同源物，也称为cdk2相关蛋白1 (CDK2AP1)，作为真正的NuRD亚基。生化和遗传分析支持MEP1、Mi2和TTK69之间的功能关联。全基因组表达分析证实TTK69、MEP1和Mi2密切合作控制转录。TTK69转录组谱与NuRD以外的重塑子相关性较差，强调了重塑子作用的选择性。在所检测的基因中，TTK69能够在没有NuRD的情况下结合染色质，但NuRD的靶向依赖于TTK69。因此，似乎存在一种等级关系，其中转录因子结合先于重塑蛋白募集。
ATP-dependent chromatin-remodeling complexes (remodelers) are essential regulators of chromatin structure and gene transcription. How remodelers can act in a gene-selective manner has remained enigmatic. A yeast two-hybrid screen for proteins binding the Drosophila transcription factor Tramtrack69 (TTK69) identified MEP1. Proteomic characterization revealed that MEP1 is a tightly associated subunit of the NuRD remodeler, harboring the Mi2 enzymatic core ATPase. In addition, we identified the fly homolog of human Deleted in oral cancer 1 (DOC1), also known as CDK2-associated protein 1 (CDK2AP1), as a bona fide NuRD subunit. Biochemical and genetic assays supported the functional association between MEP1, Mi2, and TTK69. Genomewide expression analysis established that TTK69, MEP1, and Mi2 cooperate closely to control transcription. The TTK69 transcriptome profile correlates poorly with remodelers other than NuRD, emphasizing the selectivity of remodeler action. On the genes examined, TTK69 is able to bind chromatin in the absence of NuRD, but targeting of NuRD is dependent on TTK69. Thus, there appears to be a hierarchical relationship in which transcription factor binding precedes remodeler recruitment.