SDC1 is required for proper histone H3 trimethylation by balancing the recruitment of histone methyltransferase and demethylase

Abstract

The Set1-containing complex COMPASS, which is the yeast homolog of the human MLL complex, is required for mono-, di-, and trimethylation of histone H3K4. Here, we show the molecular mechanism of COMPASS complex that regulates the methylations of histone H3K4 dependently of the phosphorylation of RNA polymerase II. We found that the deletion of SDC1, one of subunits of COMPASS, completely inverted the pattern of histone H3K4 trimethylation in actively transcribed genes. The increase of methyalation in both promoter and 3`UTR region was abrogated. Instead, in a complementary pattern, the significant increase of methylation was observed in coding region. The deletion of CTK1, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II, also reverted the pattern of histone H3K4 diimethylation as well as trimethylation. Chromatin immunopreciptation experiments further show that the phosphorylation of CTD by Kin28 or CTK1 may disrupt the recruitment of some COMPASS subunits or JmjC domain containing proteins. Taken together, our results suggest that SDC1 is required for proper histone H3 trimethylation by balancing the recruitment of histone methyltransferases and demethylase.