Lineage-specific activators affect beta-globin locus chromatin in multipotent hematopoietic progenitors.
During development, the regulated expression of tissue-specific genes can be preceded by their potentiation, that is, by chromatin activation in progenitor cells. For example, the human beta-like globin genes are potentiated in a gene- and developmental-specific manner in hematopoietic progenitors. Developmental regulation of human beta-gene expression in erythroid cells is mostly determined by transcriptional activators; however, it is not clear how gene-specific potentiation is set in hematopoietic progenitors. Using human and transgenic multipotent hematopoietic progenitors, we demonstrate that human beta-globin locus activation is characterized by TBP, NF-E2, CBP and BRG1 recruitment at both the Locus Control Region and human beta-gene promoter. Our results further indicate that in hematopoietic progenitors, EKLF influences chromatin organization at the human beta-globin locus and is instrumental for human beta-gene potentiation. Thus, we show that lineage-specific transcriptional activators expressed at basal levels in progenitor cells can participate in gene potentiation.
Bottardi
Stefania
S
Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital and Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Ross
Julie
J
Pierre-Charles
Natacha
N
Blank
Volker
V
Milot
Eric
E
D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D002843:Chromatin; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases