SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation

Masamichi Doiguchi, Takeya Nakagawa, Yuko Imamura, Mitsuhiro Yoneda, Miki Higashi, Kazuishi Kubota, Satoshi Yamashita, Hiroshi Asahara, Midori Iida, Satoshi Fujii, Tsuyoshi Ikura, Ziying Liu, Tulip Nandu, W. Lee Kraus, Hitoshi Ueda, Takashi Ito

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Abstract

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.

Original languageEnglish
Article number20179
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 18 2016

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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, W. L., Ueda, H., & Ito, T. (2016). SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation. Scientific Reports, 6, [20179]. https://doi.org/10.1038/srep20179