H3K36 trimethylation (H3K36me3) is deposited by the methyltransferase Set2, onto the nucleosomes in the transcribed regions. This protein associates with elongating RNA polymerase II. It can recruits epigenetic regulators in yeast to suppress cryptic transcription. But little is known about its role in mammals. Because in mammals, histone variant H3.3 is incorporated in gene bodies coupling with transcription. Histone H3.3-based peptides are the H3K36me3 peptides used in the biochemical studies.
Recently, some researchers from USA and China find that ZMYND11 can recognize H3.3K36me3 and regulate elongation of RNA polymerase II. ZMYND11 (also known as BS69) is a protein that functions as a co-repressor of E1A (adenovirus early region 1A) and cellular transcription factors.
It contains several histone ‘reader’ modules, including a PHD, a bromodomain and a PWWP domain. In the complex of ZMYND11 and H3.3K36me3, the H3.3-specific ‘S31’ residue and T32 are encapsulated at the bottom of the ‘bromo-ZnF-PWWP’ valley. Together with the binding of K36me3 by the PWWP aromatic cage, the binding of ZMYND11 to H3.3K36me3 is much stronger than the H3.1 counterpart.
As a candidate tumor suppressor, ZMYND11 is associated with highly expressed genes, it functions by modulating Pol II elongation. This study identified ZMYND11 as the first variant-specific reader of methylated histones. It offers a spatiotemporal control of gene expression for both normal and neoplastic growth. The importance of the histone variant H3.3 in tumor suppression is emphasized again.