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

Publication ,  Journal Article
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 ...
Published in: Nature
April 19, 2007

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 19, 2007

Volume

446

Issue

7138

Start / End Page

882 / 887

Location

England

Related Subject Headings

  • Zinc Finger E-box-Binding Homeobox 1
  • Transcriptional Activation
  • Pituitary Gland
  • Oxidoreductases, N-Demethylating
  • Mice
  • Lactotrophs
  • Kruppel-Like Transcription Factors
  • Homeodomain Proteins
  • Histone Demethylases
  • Growth Hormone
 

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Wang, J., Scully, K., Zhu, X., Cai, L., Zhang, J., Prefontaine, G. G., … Rosenfeld, M. G. (2007). Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature, 446(7138), 882–887. https://doi.org/10.1038/nature05671
Wang, Jianxun, Kathleen Scully, Xiaoyan Zhu, Ling Cai, Jie Zhang, Gratien G. Prefontaine, Anna Krones, et al. “Opposing LSD1 complexes function in developmental gene activation and repression programmes.Nature 446, no. 7138 (April 19, 2007): 882–87. https://doi.org/10.1038/nature05671.
Wang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine GG, et al. Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature. 2007 Apr 19;446(7138):882–7.
Wang, Jianxun, et al. “Opposing LSD1 complexes function in developmental gene activation and repression programmes.Nature, vol. 446, no. 7138, Apr. 2007, pp. 882–87. Pubmed, doi:10.1038/nature05671.
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. Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature. 2007 Apr 19;446(7138):882–887.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 19, 2007

Volume

446

Issue

7138

Start / End Page

882 / 887

Location

England

Related Subject Headings

  • Zinc Finger E-box-Binding Homeobox 1
  • Transcriptional Activation
  • Pituitary Gland
  • Oxidoreductases, N-Demethylating
  • Mice
  • Lactotrophs
  • Kruppel-Like Transcription Factors
  • Homeodomain Proteins
  • Histone Demethylases
  • Growth Hormone