CBX3 Regulates Efficient RNA Processing Genome Wide

HP1 alpha, beta, and gamma play an evolutionarily conserved role in the formation and maintenance of heterochromatin. In addition, some HP1 family members may also participate in transcriptional regulation of genes. Recently, HP1 gamma binding to the bodies of a subset of genes has been observed in human and murine cells. However, the generality of this phenomenon and the role HP1 gamma may play in this context are unknown. Genome-wide localization analysis reveals broad and general HP1 gamma binding at actively transcribed genes, which strongly correlates with gene activity across multiple cell types. Unexpectedly, we find HP1 gamma binding is necessary for efficient RNA processing of its target genes. Loss of HP1 gamma results in defective recruitment of splicing factors including U1-70K, and leads to accumulation of unspliced nascent transcripts genome-wide. Therefore, our data argue that the primary role of HP1 gamma is to ensure efficient RNA processing in mammalian cells. Overall design: Genome-wide localization and function of HP1 gamma in multiple cell types using ChIP-chip, ChIP-seq, and RNA-seq