title: Establishment of a cell-type-specific genetic network by the mediator complex component Med1.
abstract: The intense physiologic demand to generate vast numbers of red blood cells requires the establishment of a complex genetic network by the master regulatory transcription factor GATA-1 and its coregulators. This network dictates the genesis of enucleated erythrocytes by orchestrating the survival, proliferation, and differentiation of progenitor cells. In addition to the crucial GATA-1 coregulator Friend of GATA-1 (FOG-1), a component of the Mediator complex, Med1, facilitates GATA-1-dependent transcription at select target genes and controls erythropoiesis. It is not known to what extent Med1 contributes to GATA-1 function or whether Med1 controls a large or restricted cohort of genes that are not regulated by GATA-1. Using a genetic complementation assay in GATA-1-null erythroid cells, we demonstrate that Med1 and another Mediator component, Med25, regulate a restricted cohort of genes that are predominantly not controlled by GATA-1. Most of these genes were not regulated by Med1 in fibroblasts. Loss-of-function analyses with GATA-1-independent Med1 target genes indicate that Rrad, which encodes a small GTPase induced during human erythropoiesis, conferred erythroid cell survival. Thus, while Med1 is a context-dependent GATA-1 coregulator, it also exerts specialized functions in erythroid cells to control GATA-1-independent, cell-type-specific genes, which include candidate regulators of erythroid cell development and function.
authors: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors: Nathaniel J
authors: NJ
authors: Pope
authors: Emery H
authors: EH
authors: Bresnick
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D006224:Cricetinae; D041905:Erythroid Cells / Q000378:metabolism; D004958:Estradiol / Q000502:physiology; D050982:GATA1 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D056892:Mediator Complex / Q000502:physiology; D056913:Mediator Complex Subunit 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic; D059467:Transcriptome; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C538856:Med1 protein, mouse; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D034741:RNA, Small Interfering; C490030:Rrad protein, mouse; D004958:Estradiol; D018631:ras Proteins