CHD8是一种依赖ATP的染色质重塑因子，可调节β-连环蛋白靶基因。
CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.
作者信息
Thompson Brandi A, Tremblay Véronique, Lin Grace, Bochar Daniel A
机构信息
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
出版信息
Mol Cell Biol. 2008 Jun;28(12):3894-904. doi: 10.1128/MCB.00322-08. Epub 2008 Mar 31.
Abstract
ATP-dependent chromatin remodeling by the CHD family of proteins plays an important role in the regulation of gene transcription. Here we report that full-length CHD8 interacts directly with beta-catenin and that CHD8 is also recruited specifically to the promoter regions of several beta-catenin-responsive genes. Our results indicate that CHD8 negatively regulates beta-catenin-targeted gene expression, since short hairpin RNA against CHD8 results in the activation of several beta-catenin target genes. This regulation is also conserved through evolution; RNA interference against kismet, the apparent Drosophila ortholog of CHD8, results in a similar activation of beta-catenin target genes. We also report the first demonstration of chromatin remodeling activity for a member of the CHD6-9 family of proteins, suggesting that CHD8 functions in transcription through the ATP-dependent modulation of chromatin structure.
摘要
由CHD蛋白家族介导的ATP依赖的染色质重塑在基因转录调控中发挥重要作用。在此我们报告，全长CHD8直接与β-连环蛋白相互作用，并且CHD8也被特异性招募至多个β-连环蛋白反应性基因的启动子区域。我们的结果表明，CHD8负向调节β-连环蛋白靶向的基因表达，因为针对CHD8的短发夹RNA导致多个β-连环蛋白靶基因的激活。这种调控在进化过程中也是保守的；针对CHD8在果蝇中的明显同源物kismet进行RNA干扰，会导致β-连环蛋白靶基因的类似激活。我们还首次证明了CHD6 - 9蛋白家族成员的染色质重塑活性，这表明CHD8通过ATP依赖的染色质结构调节在转录中发挥作用。
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