Format

Send to

Choose Destination
Dev Cell. 2018 Dec 17;47(6):758-772.e5. doi: 10.1016/j.devcel.2018.11.018.

Ubiquitination-Independent Repression of PRC1 Targets during Neuronal Fate Restriction in the Developing Mouse Neocortex.

Author information

1
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
2
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: ykisi@mol.f.u-tokyo.ac.jp.
3
RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
4
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; PRESTO, JST, TokyoJapan.
5
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: ygotoh@mol.f.u-tokyo.ac.jp.

Abstract

Polycomb repressive complex (PRC) 1 maintains developmental genes in a poised state through monoubiquitination (Ub) of histone H2A. Although Ub-independent functions of PRC1 have also been suggested, it has remained unclear whether Ub-dependent and -independent functions of PRC1 operate differentially in a developmental context. Here, we show that the E3 ubiquitin ligase activity of Ring1B, a core component of PRC1, is necessary for the temporary repression of key neuronal genes in neurogenic (early-stage) neural stem or progenitor cells (NPCs) but is dispensable for the persistent repression of these genes associated with the loss of neurogenic potential in astrogliogenic (late-stage) NPCs. Our results also suggest that histone deacetylase (HDAC) activity of the NuRD/MBD3 complex and Phc2-dependent PRC1 clustering are necessary for the transition from the Ub-dependent to -independent function of PRC1. Together, these results indicate that Ub-independent mode of repression by PRC1 plays a key role in mammalian development during cell fate restriction.

KEYWORDS:

Mbd3/Nurd; Phc2–SAM clustering; Ring1B; epigenetics; histone deacetylation; monoubiquitination of histone H2A; neocortical neural stem or progenitor cells; neurogenic genes; polycomb group proteins; radial glial cells

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center