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.
Highlights
Histone acetylation plays a pivotal role in transcriptional regulation, and ATP-dependent nucleosome remodeling activity is required for optimal transcription from chromatin
We demonstrated that SMARCAD1 activates transcription together with p300/CREB-binding protein (CBP) in vivo and in vitro
P300/CBP has affinity for nucleosomes[32], once a histone octamer is wrapped with DNA, it becomes hard for histone modification enzymes to access core histones, as we have shown in Fig. 2e, lanes 2 and 6
Summary
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 Etl[1] subfamily of the Snf[2] family of helicaserelated proteins. Coactivators (SRC-1, ACTR, and TIF2)[12] Among these diverse HATs, the family members p300 and CBP are central regulators of transcription, with roles as global coactivators in higher eukaryotes. Snf[2] family members are divided into 24 distinct subfamilies, including Swr[1], EP400, INO80 and Etl[1], which belong to the swr1-like grouping, based on sequence alignment of the helicase-related regions[21]
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