SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation.
SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation.
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DOI：
10.1038/srep20179
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发表时间：
2016-02-18
影响因子：
4.6
通讯作者：
Ito T
中科院分区：
文献类型：
--
作者：
Doiguchi M;Nakagawa T;Imamura Y;Yoneda M;Higashi M;Kubota K;Yamashita S;Asahara H;Iida M;Fujii S;Ikura T;Liu Z;Nandu T;Kraus WL;Ueda H;Ito T
组蛋白乙酰化在转录调控中起着关键作用，而依赖于ATP的核小体重塑活性是染色质最佳转录所必需的。虽然这两项活动的特点已经很好，但它们如何协调仍有待确定。我们在果蝇核抽提物中发现了依赖于ATP的组蛋白H_2A乙酰化活性。该活性经柱层析纯化，证明是由解旋酶相关蛋白Snf2家族中Etl1亚家族的CREB结合蛋白(CBP)和SMARCAD1的酶活性组成。SMARCAD1通过CBP以ATP依赖的方式促进核小体中H_2A、K_5和K_8的乙酰化。对异位表达SMARCAD1的S2细胞的表达阵列分析显示，基因上调。利用这些上调基因的天然基因组模板，我们发现SMARCAD1在体外激活了它们的转录。SMARCAD1和CBP的敲除分析表明存在重叠的基因控制，而对这些共同控制的基因进行的CHIP-SEQ分析表明，CBP在SMARCAD1之前被招募到启动子。此外，果蝇的遗传学实验表明，SMARCAD1/Etl1和CBP/nej在发育过程中存在相互作用。SMARCAD1的重塑活性和组蛋白被CBP乙酰化之间的相互作用揭示了染色质的功能和基因组完整性网络。
Histone acetylation plays a pivotal role in transcriptional regulation, and ATP-dependent nucleosome remodeling activity is required for optimal transcription from chromatin. While these two activities have been well characterized, how they are coordinated remains to be determined. We discovered ATP-dependent histone H2A acetylation activity in Drosophila nuclear extracts. This activity was column purified and demonstrated to be composed of the enzymatic activities of CREB-binding protein (CBP) and SMARCAD1, which belongs to the Etl1 subfamily of the Snf2 family of helicase-related proteins. SMARCAD1 enhanced acetylation by CBP of H2A K5 and K8 in nucleosomes in an ATP-dependent fashion. Expression array analysis of S2 cells having ectopically expressed SMARCAD1 revealed up-regulated genes. Using native genome templates of these up-regulated genes, we found that SMARCAD1 activates their transcription in vitro. Knockdown analysis of SMARCAD1 and CBP indicated overlapping gene control, and ChIP-seq analysis of these commonly controlled genes showed that CBP is recruited to the promoter prior to SMARCAD1. Moreover, Drosophila genetic experiments demonstrated interaction between SMARCAD1/Etl1 and CBP/nej during development. The interplay between the remodeling activity of SMARCAD1 and histone acetylation by CBP sheds light on the function of chromatin and the genome-integrity network.