Pluto Bioinformatics

GSE144862: HP1 regulates H3K36 methylation and pluripotency in embryonic stem cells (RNA-seq)

Bulk RNA sequencing

The heterochromatin protein 1 (HP1) family members are canonical effectors and propagators of gene repression mediated by histone H3 lysine 9 (H3K9) methylation. HP1 exhibits an increased interaction with active transcription elongation-associated factors in embryonic stem cells (ESCs) compared to somatic cells. However, whether this association has a functional consequence remains elusive. Here we find that genic HP1 colocalizes and enhances enrichment of transcription elongation-associated H3K36me3 rather than H3K9me3. Unexpectedly, sustained H3K36me3 deposition is dependent on HP1. HP1-deleted ESCs display reduced H3K36me3 enrichment, concomitant with decreased expression at shared genes which function to maintain cellular homeostasis. Both the H3K9me3-binding chromodomain and histone binding ability of HP1 are dispensable for maintaining H3K36me3 levels. Instead, the chromoshadow together with the hinge domain of HP1 that confer protein and nucleic acid-binding ability are sufficient because they retain the ability to interact with NSD1, an H3K36 methyltransferase. HP1-deleted ESCs have a slower self-renewal rate and an impaired ability to differentiate towards cardiac mesoderm. Our findings reveal a requirement for HP1 in faithful establishment of transcription elongation in ESCs, which regulates pluripotency. SOURCE: Rupa Sridharan (rsridharan2@wisc.edu) - Sridharan University of Wisconsin