UC Santa Cruz

Polycomb and trithorax group proteins play highly conserved roles in cell fate maintenance by affecting gene expression during development. Acting at the level of chromatin regulation, Polycomb group proteins repress transcription while trithorax group proteins promote transcription. My research has focused on the function of the trithorax group protein Kismet (KIS) in Drosophila. KIS is a member of the CHD family of ATP-dependent chromatin-remodeling factors and is related to CHD7, a human protein linked to CHARGE syndrome. KIS maintains HOX gene transcription and facilitates global transcription elongation in Drosophila. In this work, I examined how KIS interacts with other trithorax group proteins to maintain active states of transcription. I found that KIS promotes the localization of the trithorax group histone methyltransferases ASH1 and TRX to chromatin, which antagonizes the methylation of histone H3 on lysine 27 (H3K27) by Polycomb group proteins. KIS recruits ASH1 to chromatin and antagonizes H3K27 methylation independently of its role in facilitating transcription elongation. Finally, I examined the mechanism by which ASH1 counteracts H3K27 methylation and found evidence that ASH1 dimethylates histone H3 on lysine 36 (H3K36) in vivo. My work indicates that KIS plays an important role in coordinating the function of trithorax group histone methyltransferases to antagonize Polycomb group repression by counteracting H3K27 methylation.