Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
Shannon M McNulty
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Zachary Duda
Department of Molecular and Cell Biology, University of Connecticut, Storrs, United States; Institute for Systems Genomics, University of Connecticut, Storrs, United States
Rachel J O’Neill
Department of Molecular and Cell Biology, University of Connecticut, Storrs, United States; Institute for Systems Genomics, University of Connecticut, Storrs, United States
Heterochromatin formed by the SUV39 histone methyltransferases represses transcription from repetitive DNA sequences and ensures genomic stability. How SUV39 enzymes localize to their target genomic loci remains unclear. Here, we demonstrate that chromatin-associated RNA contributes to the stable association of SUV39H1 with constitutive heterochromatin in human cells. We find that RNA associated with mitotic chromosomes is concentrated at pericentric heterochromatin, and is encoded, in part, by repetitive α-satellite sequences, which are retained in cis at their transcription sites. Purified SUV39H1 directly binds nucleic acids through its chromodomain; and in cells, SUV39H1 associates with α-satellite RNA transcripts. Furthermore, nucleic acid binding mutants destabilize the association of SUV39H1 with chromatin in mitotic and interphase cells – effects that can be recapitulated by RNase treatment or RNA polymerase inhibition – and cause defects in heterochromatin function. Collectively, our findings uncover a previously unrealized function for chromatin-associated RNA in regulating constitutive heterochromatin in human cells.
