title: SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation.
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.
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Doiguchi
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Higashi
authors.affiliation: Daiichi Sankyo RD Novare CO., LTD., Tokyo 134-8630, Japan.
authors.forename: Kazuishi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
authors.affiliation: Kyushu Institute of Technology, Fukuoka 820-8502, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Iida
authors.affiliation: Kyushu Institute of Technology, Fukuoka 820-8502, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.affiliation: UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Tulip
authors.initials: T
authors.lastname: Nandu
authors.affiliation: UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
authors.affiliation: Okayama University, Okayama 700-8530, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D006657:Histones; C524696:nej protein, Drosophila; D050880:p300-CBP Transcription Factors; D004265:DNA Helicases