Arrestin´ the Regulator of Regulators: β-arrestin1 Initiates Hematopoiesis through Relieving PcG Repression

A group of biologists at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), CAS, lately report on the Oct. 30th issue of Cell that Polycomb group (PcG) proteins -mediated silencing is regulated by β-arrestin1.

 

Polycomb group (PcG) proteins are evolutionarily conserved transcriptional repressors involved in numerous biological processes, such as stem cell self-renewal, genomic imprinting and X chromosome inactivation. In mouse and human embryonic stem cells, PcG proteins dynamically bind to and silence a large cohort of developmental regulators, acting as the "regulator of regulators". However, However, the mechanisms by which PcG proteins are dynamically regulated remain poorly understood. Thus, discovery of novel regulators of PcG proteins is of great importance to the study of PcG-mediated epigenetic regulation and biological processes.

 

Latest studies from a SIBCB group led by Prof. PEI Gang, a CAS Member, shed new light on the dynamic regulation of PcG proteins during vertebrate development. In their studies, Yue et al. found that an important signal protein called β-arrestin 1 is evolutionarily conserved in zebrafish. Embryos depleted of β-arrestin1 showed significant defects in primitive hematopoiesis, which could be attributed to the disruption of cdx4-hox pathway during early embryogenesis. Mechanistic analysis revealed that PcG recruitment by YY1 contributes to the epigenetic silencing of cdx4-hox pathway, while the correct expression of β-arrestin1 sequesters YY1 and relieves PcG repression, thus specifying hematopoietic lineage commitment.

 

By this very impressive piece of work, as commented by the reviewers, Pei and his colleagues not only demonstrate an unexpected role of β-arrestin1 during vertebrate development, but also offer new insights into the mechanism of PcG protein regulation.

 

This research was supported by National Zebrafish Resources of China, and grants from the Ministry of Science and Technology, National Natural Science Foundation of China, Shanghai Municipal Commission for Science and Technology, and Chinese Academy of Sciences.