Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genes Dev. 2009 Apr 1;23(7):837-48. doi: 10.1101/gad.1769609.

A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal.

Author information

  • 1Howard Hughes Medical Institute, Department of Genetics, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

We performed a genome-wide siRNA screen in mouse embryonic stem (ES) cells to identify genes essential for self-renewal, and found 148 genes whose down-regulation caused differentiation. Many of the identified genes function in gene regulation and/or development, and are highly expressed in ES cells and embryonic tissues. We further identified target genes of two transcription regulators Cnot3 and Trim28. We discovered that Cnot3 and Trim28 co-occupy many putative gene promoters with c-Myc and Zfx, but not other pluripotency-associated transcription factors. They form a unique module in the self-renewal transcription network, separate from the core module formed by Nanog, Oct4, and Sox2. The transcriptional targets of this module are enriched for genes involved in cell cycle, cell death, and cancer. This supports the idea that regulatory networks controlling self-renewal in stem cells may also be active in certain cancers and may represent novel anti-cancer targets. Our screen has implicated over 100 new genes in ES cell self-renewal, and illustrates the power of RNAi and forward genetics for the systematic study of self-renewal.

PMID:
19339689
[PubMed - indexed for MEDLINE]
PMCID:
PMC2666338
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk