title: Transcriptional mechanisms underlying hemoglobin synthesis.
abstract: The physiological switch in expression of the embryonic, fetal, and adult β-like globin genes has garnered enormous attention from investigators interested in transcriptional mechanisms and the molecular basis of hemoglobinopathies. These efforts have led to the discovery of cell type-specific transcription factors, unprecedented mechanisms of transcriptional coregulator function, genome biology principles, unique contributions of nuclear organization to transcription and cell function, and promising therapeutic targets. Given the vast literature accrued on this topic, this article will focus on the master regulator of erythroid cell development and function GATA-1, its associated proteins, and its frontline role in controlling hemoglobin synthesis. GATA-1 is a crucial regulator of genes encoding hemoglobin subunits and heme biosynthetic enzymes. GATA-1-dependent mechanisms constitute an essential regulatory core that nucleates additional mechanisms to achieve the physiological control of hemoglobin synthesis.
authors.affiliation: Department of Cell and Regenerative Biology, UW-Madison Blood Research Program, Wisconsin Institute for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705.
authors.forename: Koichi R
authors.initials: KR
authors.lastname: Katsumura
authors.forename: Andrew W
authors.initials: AW
authors.lastname: DeVilbiss
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Pope
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Johnson
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology*; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D006453:Hemoglobinopathies / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D014157:Transcription Factors / Q000502:physiology; D055544:beta-Globins / Q000096:biosynthesis / Q000235:genetics
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D050982:GATA1 Transcription Factor; D006454:Hemoglobins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C498432:ZFPM1 protein, human; D055544:beta-Globins; C080774:erythroid Kruppel-like factor; D005319:Fetal Hemoglobin