4N4H

Crystal structure of the Bromo-PWWP of the mouse zinc finger MYND-type containing 11 isoform alpha in complex with histone H3.1K36me3

4N4H の概要

• エントリーDOI: 10.2210/pdb4n4h/pdb
• 関連するPDBエントリー: 4N4G 4N4I
• 分子名称: Zinc finger MYND domain-containing protein 11, Peptide from Histone H3.1, ZINC ION, ... (6 entities in total)
• 機能のキーワード: tandem bromodomain-zinc finger-pwwp motif, histone h3.3-specific, transcription
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Nucleus : Q8R5C8 P68431
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32172.09

構造登録者

Li, Y.,Ren, Y.,Li, H. (登録日: 2013-10-08, 公開日: 2014-03-05, 最終更新日: 2023-11-08)

主引用文献

Wen, H.,Li, Y.,Xi, Y.,Jiang, S.,Stratton, S.,Peng, D.,Tanaka, K.,Ren, Y.,Xia, Z.,Wu, J.,Li, B.,Barton, M.C.,Li, W.,Li, H.,Shi, X.
ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression
Nature, 508:263-268, 2014

PubMed Abstract: Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.

PubMed: 24590075
DOI: 10.1038/nature13045

実験手法

X-RAY DIFFRACTION (2.302 Å)