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Submitted on October 22, 2004
Accepted on December 16, 2004
Department of Medicine, Mount Sinai Hospital and University of Toronto; Department of Pathology, University Health Network and University of Toronto; The Freeman Centre for Endocrine Oncology and The Ontario Cancer Institute, 610 University Avenue, Toronto; Ontario, Canada M5G 2M9; Department of Medicine, Mount Sinai Hospital and University of Toronto; Department of Pathology, University Health Network and University of Toronto; The Freeman Centre for Endocrine Oncology and The Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
* To whom correspondence should be addressed. E-mail: sylvia.asa{at}uhn.on.ca.
The Ikaros transcription factors play critical functions in the control of lympho-hematopoiesis and immune regulation. Family members contain multiple zinc fingers that mediate DNA binding but have also been implicated as part of a complex chromatin remodeling network. We show here that Ikaros is expressed in pituitary mammosomatotrophs where it regulates the GH (GH) and prolactin (PRL) genes. Ikaros was detected by Northern and western blotting in GH4 pituitary mammosomatotroph cells. Wild-type Ikaros (Ik1) inhibits GH mRNA and protein expression while stimulating PRL mRNA and protein levels. Ikaros does not bind directly to the proximal GH promoter but abrogates the effect of the histone deacetylation inhibitor trichostatin-A on this region. Ikaros selectively deacetylates histone 3 residues on the proximal transfected or endogenous GH promoter and limits access of the Pit1 activator. In contrast, Ikaros acetylates histone 3 on the proximal PRL promoter and facilitates Pit1 binding to this region in the same cells. These data provide evidence for Ikaros mediated-histone acetylation and chromatin remodeling in the selective regulation of pituitary GH and PRL hormone gene expression.
This article has been cited by other articles:
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  X. Zhu, S. L. Asa, and S. Ezzat Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary Mol. Endocrinol., May 1, 2007; 21(5): 1205 - 1215. [Abstract] [Full Text] [PDF]
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S. Ezzat, X. Zhu, S. Loeper, S. Fischer, and S. L. Asa Tumor-Derived Ikaros 6 Acetylates the Bcl-XL Promoter to Up-Regulate a Survival Signal in Pituitary Cells Mol. Endocrinol., November 1, 2006; 20(11): 2976 - 2986. [Abstract] [Full Text] [PDF]
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 S. Ezzat, R. Mader, S. Fischer, S. Yu, C. Ackerley, and S. L. Asa An essential role for the hematopoietic transcription factor Ikaros in hypothalamic-pituitary-mediated somatic growth PNAS, February 14, 2006; 103(7): 2214 - 2219. [Abstract] [Full Text] [PDF]
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