Histone posttranslational modification leads to downstream effects indirectly by allowing or preventing docking of effector molecules, or directly by changing the intrinsic biophysical properties of local chromatin. To date, little has been done to study posttranslational modifications that lie outside of the unstructured tail domains of histones. Core residues, and in particular arginines in H3 and H4, mediate key interactions between the histone octamer and DNA in forming the nucleosomal particle. Using mass spectrometry, we find that one of these core residues, arginine 42 of histone H3 (H3R42), is dimethylated in mammalian cells by the methyltransferases coactivator arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo, and we demonstrate that methylation of H3R42 stimulates transcription in vitro from chromatinized templates. Thus, H3R42 is a new, "nontail" histone methylation site with positive effects on transcription. We propose that methylation of basic histone residues at the DNA interface may disrupt histone:DNA interactions, with effects on downstream processes, notably transcription.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Sep 10 2013|