Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus.
Enhancers can regulate designate promoters over long distances by forming chromatin loops. Whether chromatin loops are lost or reconfigured during gene repression is largely unexplored. We examined the chromosome conformation of the Kit gene that is expressed during early erythropoiesis but is downregulated upon cell maturation. Kit expression is controlled by sequential occupancy of two GATA family transcription factors. In immature cells, a distal enhancer bound by GATA-2 is in physical proximity with the active Kit promoter. Upon cell maturation, GATA-1 displaces GATA-2 and triggers a loss of the enhancer/promoter interaction. Moreover, GATA-1 reciprocally increases the proximity in nuclear space among distinct downstream GATA elements. GATA-1-induced transitions in chromatin conformation are not simply the consequence of transcription inhibition and require the cofactor FOG-1. This work shows that a GATA factor exchange reconfigures higher-order chromatin organization, and suggests that de novo chromatin loop formation is employed by nuclear factors to specify repressive outcomes.
Jing
Huie
H
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Vakoc
Christopher R
CR
Ying
Lei
L
Mandat
Sean
S
Wang
Hongxin
H
Zheng
Xingwu
X
Blobel
Gerd A
GA
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D040641:Quantitative Trait Loci / Q000502:physiology*; D020218:Response Elements / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse; D019009:Proto-Oncogene Proteins c-kit