title: Coregulation of genetic programs by the transcription factors NFIB and STAT5.
abstract: Mammary-specific genetic programs are activated during pregnancy by the common transcription factor signal transducer and activator of transcription (STAT) 5. More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs that coincide with STAT5 in vivo binding, suggesting functional synergy between these two transcription factors. The role of NFIB in this governance was investigated in mice from which Nfib had been inactivated in mammary stem cells or in differentiating alveolar epithelium. Although NFIB was not required for alveolar expansion, the combined absence of NFIB and STAT5 prevented the formation of functional alveoli. NFIB controlled the expression of mammary-specific and STAT5-regulated genes and chromatin immunoprecipitation-sequencing established STAT5 and NFIB binding at composite regulatory elements containing histone H3 lysine dimethylation enhancer marks and progesterone receptor binding. By integrating previously published chromatin immunoprecipitation-sequencing data sets, the presence of NFIB-STAT5 modules in other cell types was investigated. Notably, genomic sites bound by NFIB in hair follicle stem cells were also occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many of these genes were under NFIB control in both hair follicle stem cells and mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs.
authors.affiliation: Laboratory of Genetics and Physiology (G.W.R., K.K., K.H.Y., Y.T., D.Y., V.C., S.J.J., L.H.), National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Department of Microbiology (K.K.), Dankook University, Cheonan 330-714, Republic of Korea; Chengdu University of Traditional Chinese Medicine (Y.T.), Chengdu 610072, Republic of China; Key Laboratory of Acupuncture and Medicine (B.-M.Z.), Nanjing University of Traditional Chinese Medicine, Nanjing 210046, Republic of China; and New York State Center of Excellence in Bioinformatics and Life Sciences (R.M.G.), Department of Biochemistry, Developmental Genomics Group, University at Buffalo, Buffalo, New York 14203.
authors.forename: Gertraud W
authors.initials: GW
authors.lastname: Robinson
authors.forename: Keunsoo
authors.initials: K
authors.lastname: Kang
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Yoo
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Bing-Mei
authors.initials: BM
authors.lastname: Zhu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamaji
authors.forename: Vera
authors.initials: V
authors.lastname: Colditz
authors.forename: Seung Jian
authors.initials: SJ
authors.lastname: Jang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D005260:Female; D005786:Gene Expression Regulation; D063990:Gene Ontology; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology; D008819:Mice, Nude; D008822:Mice, Transgenic; D051839:NFI Transcription Factors / Q000502:physiology*; D011247:Pregnancy; D050799:STAT5 Transcription Factor / Q000502:physiology*; D059467:Transcriptome
chemical_list: D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; D050799:STAT5 Transcription Factor