Histone variant H3.3-specific readout of H3K36 trimethylation by ZMYND11 links transcription elongation control to tumour suppression
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE48423 |
| Title | Histone variant H3.3-specific readout of H3K36 trimethylation by ZMYND11 links transcription elongation control to tumour suppression |
| Description | Recognition of modified histones by reader proteins plays a critical role in the regulation of transcription1. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions following RNA polymerase II (Pol II) elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin at an appropriate state to suppress cryptic transcription2,3. 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 bodies4. Here we show that the candidate tumor suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates Pol II elongation. Structural studies reveal 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 Ser31 residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. ChIP-sequencing analysis reveal a genome-wide colocalization 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 corepressor via modulating the transition of the promoter-proximal paused Pol II to elongation. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumor cell growth; higher expression of ZMYND11 is observed in triple-negative breast cancer patients with better prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth and tumor 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 tumor suppression. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48423 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE55534
Rate of elongation by RNA polymerase II is influenced by specific gene features and histone modifications
1
GSE62171
RNA Polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA Polymerase II
1
GSE63314
Stably-paused genes revealed through inhibition of transcription initiation by the TFIIH inhibitor Triptolide
1
GSE70355
Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
