Dynamic regulation of Gata factor levels is more important than their identity.
Three Gata transcription factors (Gata1, -2, and -3) are essential for hematopoiesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythroid cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gata1, -2, and -3 transgenes driven by beta-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements.
Ferreira
Rita
R
Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
Wai
Albert
A
Shimizu
Ritsuko
R
Gillemans
Nynke
N
Rottier
Robbert
R
von Lindern
Marieke
M
Ohneda
Kinuko
K
Grosveld
Frank
F
Yamamoto
Masayuki
M
Philipsen
Sjaak
S
D000818:Animals; D004920:Erythropoiesis; D050980:GATA Transcription Factors / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000172:deficiency; D050989:GATA2 Transcription Factor / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D019076:Transgenes
D050980:GATA Transcription Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D012333:RNA, Messenger