Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility

作者：Musselman Catherine A; Gibson Matthew D; Hartwick Erik W; North Justin A; Gatchalian Jovylyn; Poirier Michael G; Kutateladze Tatiana G^*

来源：Nature Communications, 2013, 4(1): 2969.

DOI：10.1038/ncomms3969

The Tudor domain of human PHF1 recognizes trimethylated lysine 36 of histone H3 (H3K36me3). This interaction modulates the methyltransferase activity of the PRC2 complex and has a role in retention of PHF1 at DNA damage sites. We have previously determined the structural basis for the association of Tudor with a methylated histone peptide. Here we detail the molecular mechanism of binding of the Tudor domain to the H3K(C)36me3-nucleosome core particle (H3K(C)36me3-NCP). Using a combination of TROSY NMR and FRET, we show that Tudor concomitantly interacts with H3K36me3 and DNA. Binding of the PHF1 Tudor domain to the H3K(C)36me3-NCP stabilizes the nucleosome in a conformation in which the nucleosomal DNA is more accessible to DNA-binding regulatory proteins. Our data provide a mechanistic explanation for the consequence of reading of the active mark H3K36me3 by the PHF1 Tudor domain.

• 出版日期2013-12