Opposing LSD1 complexes function in developmental gene activation and repression programmes.

Published

Journal Article

Precise control of transcriptional programmes underlying metazoan development is modulated by enzymatically active co-regulatory complexes, coupled with epigenetic strategies. One thing that remains unclear is how specific members of histone modification enzyme families, such as histone methyltransferases and demethylases, are used in vivo to simultaneously orchestrate distinct developmental gene activation and repression programmes. Here, we report that the histone lysine demethylase, LSD1--a component of the CoREST-CtBP co-repressor complex--is required for late cell-lineage determination and differentiation during pituitary organogenesis. LSD1 seems to act primarily on target gene activation programmes, as well as in gene repression programmes, on the basis of recruitment of distinct LSD1-containing co-activator or co-repressor complexes. LSD1-dependent gene repression programmes can be extended late in development with the induced expression of ZEB1, a Krüppel-like repressor that can act as a molecular beacon for recruitment of the LSD1-containing CoREST-CtBP co-repressor complex, causing repression of an additional cohort of genes, such as Gh, which previously required LSD1 for activation. These findings suggest that temporal patterns of expression of specific components of LSD1 complexes modulate gene regulatory programmes in many mammalian organs.

Full Text

Duke Authors

Cited Authors

  • Wang, J; Scully, K; Zhu, X; Cai, L; Zhang, J; Prefontaine, GG; Krones, A; Ohgi, KA; Zhu, P; Garcia-Bassets, I; Liu, F; Taylor, H; Lozach, J; Jayes, FL; Korach, KS; Glass, CK; Fu, X-D; Rosenfeld, MG

Published Date

  • April 19, 2007

Published In

Volume / Issue

  • 446 / 7138

Start / End Page

  • 882 - 887

PubMed ID

  • 17392792

Pubmed Central ID

  • 17392792

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature05671

Language

  • eng

Conference Location

  • England