title: Context-dependent function of "GATA switch" sites in vivo.
abstract: Master transcriptional regulators of development often function through dispersed cis elements at endogenous target genes. While cis-elements are routinely studied in transfection and transgenic reporter assays, it is challenging to ascertain how they function in vivo. To address this problem in the context of the locus encoding the critical hematopoietic transcription factor Gata2, we engineered mice lacking a cluster of GATA motifs 2.8 kb upstream of the Gata2 transcriptional start site. We demonstrate that the -2.8 kb site confers maximal Gata2 expression in hematopoietic stem cells and specific hematopoietic progenitors. By contrast to our previous demonstration that a palindromic GATA motif at the neighboring -1.8 kb site maintains Gata2 repression in terminally differentiating erythroid cells, the -2.8 kb site was not required to initiate or maintain repression. These analyses reveal qualitatively distinct functions of 2 GATA motif-containing regions in vivo.
authors.affiliation: Division of Hematology-Oncology, Children's Hospital Boston, Boston, MA, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Snow
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Trowbridge
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Johnson
authors.forename: Tohru
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Nikla E
authors.initials: NE
authors.lastname: Emambokus
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Grass
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D050989:GATA2 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D055879:Gene Knock-In Techniques; D005812:Genes, Switch; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; D011994:Recombinant Proteins