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Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility.

ABSTRACT: 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 H3KC36me3-nucleosome core particle (H3KC36me3-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 H3KC36me3-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.

SUBMITTER: Musselman CA

PROVIDER: S-EPMC4007151 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility.

Musselman Catherine A CA Gibson Matthew D MD Hartwick Erik W EW North Justin A JA Gatchalian Jovylyn J Poirier Michael G MG Kutateladze Tatiana G TG

Nature communications 20130101

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 H3KC36me3-nucleosome core particle (H3KC36me3-NCP). Using a combination of TROSY ...[more]

PMID: 24352064

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