title: The zinc finger Ikaros transcription factor regulates pituitary growth hormone and prolactin gene expression through distinct effects on chromatin accessibility.
abstract: The Ikaros transcription factors perform critical functions in the control of lymphohematopoiesis 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 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 but stimulates 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.
authors.affiliation: Department of Medicine, Mount Sinai Hospital and University of Toronto, Ontario, Canada.
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: Shunjiang
authors.initials: S
authors.lastname: Yu
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051740:Ikaros Transcription Factor; D051379:Mice; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D051740:Ikaros Transcription Factor; D011388:Prolactin; D012333:RNA, Messenger; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat; C497238:Zfpn1a1 protein, mouse; C012589:trichostatin A