Identification of a novel PRC2 recruiter in mammalian cells
Master of Science
Polycomb repressive complex (PRC) 2 functions to repress thousands of target genes, and they are responsible for stem cell differentiation and carcinogenesis. However, how PRC2 are recruited to specific regions of their target genes remains elusive. In Drosophila, nine sequence-specific transcription factors including Zeste have been shown to act as PRC2 recruiters, but little is known about their homologues in mammalian cells, as a straightforward homology search failed to work in most cases. Aided by three-dimensional structure prediction and the use of the genomes of intermediate bridging species, we have identified a new protein, Zeste Homologue in humans (ZH), as the human homologue of Drosophila Zeste. Gel shift assays indicated that ZH binds to Zeste recognition sequence via its N-terminal DNA binding domain. ZH physically interacted with the components of PRC2 in GST-pull down assays. Chip-seq and Chip-qPCR experiments show the co-localization of ZH and PRC2 complex. Together, these findings revealed the critical function of ZH in recruiting PRC2 complexes to their target genes.
ZH; PRC2; Zeste