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Sci Rep. 2016 Feb 18;6:20179. doi: 10.1038/srep20179.

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

Author information

1
Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
2
Daiichi Sankyo RD Novare CO., LTD., Tokyo 134-8630, Japan.
3
Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
4
Kyushu Institute of Technology, Fukuoka 820-8502, Japan.
5
Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
6
UT Southwestern Medical Center, Dallas, TX, 75390, USA.
7
Okayama University, Okayama 700-8530, Japan.

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.

PMID:
26888216
PMCID:
PMC4757861
DOI:
10.1038/srep20179
[Indexed for MEDLINE]
Free PMC Article

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