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 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.
Zhu
Xuegong
X
Department of Medicine, Mount Sinai Hospital and University of Toronto, Canada.
Asa
Sylvia L
SL
Ezzat
Shereen
S
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification
D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D051740:Ikaros Transcription Factor; D004247:DNA; D006655:Histone Deacetylases