title: A large gene network in immature erythroid cells is controlled by the myeloid and B cell transcriptional regulator PU.1.
abstract: PU.1 is a hematopoietic transcription factor that is required for the development of myeloid and B cells. PU.1 is also expressed in erythroid progenitors, where it blocks erythroid differentiation by binding to and inhibiting the main erythroid promoting factor, GATA-1. However, other mechanisms by which PU.1 affects the fate of erythroid progenitors have not been thoroughly explored. Here, we used ChIP-Seq analysis for PU.1 and gene expression profiling in erythroid cells to show that PU.1 regulates an extensive network of genes that constitute major pathways for controlling growth and survival of immature erythroid cells. By analyzing fetal liver erythroid progenitors from mice with low PU.1 expression, we also show that the earliest erythroid committed cells are dramatically reduced in vivo. Furthermore, we find that PU.1 also regulates many of the same genes and pathways in other blood cells, leading us to propose that PU.1 is a multifaceted factor with overlapping, as well as distinct, functions in several hematopoietic lineages.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Sandeep N
authors.initials: SN
authors.lastname: Wontakal
authors.forename: Xingyi
authors.initials: X
authors.lastname: Guo
authors.forename: Britta
authors.initials: B
authors.lastname: Will
authors.forename: Minyi
authors.initials: M
authors.lastname: Shi
authors.forename: Debasish
authors.initials: D
authors.lastname: Raha
authors.forename: Milind C
authors.initials: MC
authors.lastname: Mahajan
authors.forename: Sherman
authors.initials: S
authors.lastname: Weissman
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Skoultchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism; D053263:Gene Regulatory Networks; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1