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Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation


Klein, BJ; Jang, SM; Lachance, C; Mi, W; Lyu, J; Sakuraba, S; Krajewski, K; Wang, WW; Sidoli, S; Liu, J; Zhang, Y; Wang, X; Warfield, BM; Kueh, AJ; Voss, AK; Thomas, T; Garcia, BA; Liu, WR; Strahl, BD; Kono, H; Li, W; Shi, X; Cote, J; Kutateladze, TG
2019-10-17
Nature Communications
Journal Article
10
1
4724
Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.
Springer Nature
Blood Cells and Blood Cancer; Epigenetics and Development
10.1038/s41467-019-12551-5
31624313
Refer to article for additional funding acknowledgements
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Creation Date 2019-10-28 12:05:03 Last Modified 2019-10-30 09:36:57