Activation of RNA polymerase I transcription by Cockayne syndrome group B protein and histone methyltransferase G9a

Cockayne syndrome group B (CSB) protein plays a role in both transcription-coupled DNA repair and transcriptional regulation of all three classes of nuclear RNA polymerases. Here we show that a complex consisting of CSB, RNA polymerase I (Pol I), and histone methyltransferase G9a is present at active rRNA genes. G9a methylates histone H3 on lysine 9 (H3K9me2) in the pre-rRNA coding region and facilitates the association of heterochromatin protein 1 gamma (HP1 gamma) with rDNA. Both H3K9 methylation and HP1 gamma association require ongoing transcription. Knockdown of CSB prevents the association of Pol I with rDNA, impairs the interaction of G9a with Pol 1, and inhibits pre-rRNA synthesis. Likewise, knockdown of G9a leads to decreased levels of H3K9me2 in the transcribed region and downregulation of pre-rRNA synthesis. The results reveal the mechanism underlying CSB-mediated activation of rDNA transcription and link G9a-dependent H3K9 methylation to Pol I transcription elongation through chromatin.