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A Critical Role for the Co-Repressor N-CoR in Erythroid Differentiation and Heme Synthesis
Cell Research
  • Dianzheng Zhang, Philadelphia College of Osteopathic Medicine
  • Ellen Cho, Philadelphia College of Osteopathic Medicine
  • Jiemin Wong
Document Type
Article
Publication Date
9-1-2007
Abstract

Co-repressor N-CoR (nuclear receptor co-repressor) has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal and appear to die from anemia owing to defects in definitive erythropoiesis. However, the underlying molecular mechanisms of N-CoR-mediated erythroid differentiation are largely unknown. Using the human erythroleukemic K562 cell line, which can be chemically induced to differentiate into either erythroid or megakaryocytic lineages depending on the inducers used, we have investigated the role of N-CoR in erythroid differentiation. We show that knockdown of N-CoR either transiently (siRNA) or permanently (shRNA) impairs the cytosine arabinoside (Ara-C)- but not hemin-induced erythroid differentiation of K562 cells. RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase (ALA-S2), a key enzyme involved in heme biosynthesis. Furthermore, the amount of N-CoR proteins increases significantly during Ara-C-induced K562 differentiation, apparently through a post-transcriptional mechanism. Consistent with the data from N-CoR-null mice, N-CoR is not required for the differentiation of K562 cells into megakaryocytic lineages, induced by phorbol 12-myristate 13-acetate. Thus, our in vitro study confirms a role for N-CoR in erythroid differentiation and reveals for the first time that N-CoR is required for the induction of a key enzyme involved in heme synthesis.

PubMed ID
16717366
Comments

This article was published in Cell Research, Volume 17, Issue 9, September 2007, Pages 804-814.

The published version is available at http://dx.doi.org/10.1038/cr.2007.72

Copyright © 2007 Shanghai Institutes for Biological Sciences

Citation Information
Dianzheng Zhang, Ellen Cho and Jiemin Wong. "A Critical Role for the Co-Repressor N-CoR in Erythroid Differentiation and Heme Synthesis" Cell Research Vol. 17 Iss. 9 (2007) p. 804 - 814
Available at: http://works.bepress.com/dianzheng_zhang/9/