Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary

The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2007-05, Vol.21 (5), p.1205-1215
Main Authors: Zhu, Xuegong, Asa, Sylvia L, Ezzat, Shereen
Format: Article
Language:English
Subjects:
Animals
Base Sequence
DNA - genetics
DNA Methylation
Exons
Female
Gene Expression Regulation
Histone Deacetylase Inhibitors
Histone Deacetylases - metabolism
Humans
Ikaros Transcription Factor - genetics
Male
Mice
Molecular Sequence Data
Pituitary Gland - physiology
RNA, Messenger - genetics
RNA, Messenger - isolation & purification
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Summary:The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros’ role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2007-0053