EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis.
The Krüppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Krüppel-like factor (EKLF or KLF1) regulates adult beta-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and betah1-, but not adult betaglobin, gene expression in mice. Both EKLF and KLF2 play roles in primitive erythroid cell development. To investigate potential interactions between these genes, EKLF/KLF2 double-mutant embryos were analyzed. EKLF(-/-)KLF2(-/-) mice appear anemic at embryonic day 10.5 (E10.5) and die before E11.5, whereas single-knockout EKLF(-/-) or KLF2(-/-) embryos are grossly normal at E10.5 and die later than EKLF(-/-)KLF2(-/-) embryos. At E10.5, Ey- and betah1-globin mRNA is greatly reduced in EKLF(-/-)KLF2(-/-), compared with EKLF(-/-) or KLF2(-/-) embryos, consistent with the observed anemia. Light and electron microscopic analyses of E9.5 EKLF(-/-)KLF2(-/-) yolk sacs, and cytospins, indicate that erythroid and endothelial cells are morphologically more abnormal than in either single knockout. EKLF(-/-)KLF2(-/-) erythroid cells are markedly irregularly shaped, suggesting membrane abnormalities. EKLF and KLF2 may have coordinate roles in a common progenitor to erythroid and endothelial cells. The data indicate that EKLF and KLF2 have redundant functions in embryonic beta-like globin gene expression, primitive erythropoiesis, and endothelial development.
Department of Human Genetics, and Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Richmond, VA 23298, USA.
Priyadarshi
P
Basu
Tina K
TK
Lung
Wafaa
W
Lemsaddek
Thanh Giang
TG
Sargent
David C
DC
Williams
Mohua
M
Basu
Latasha C
LC
Redmond
Jerry B
JB
Lingrel
Jack L
JL
Haar
Joyce A
JA
Lloyd
D000740:Anemia / Q000196:embryology / Q000235:genetics / Q000473:pathology; D000818:Animals; D004622:Embryo, Mammalian; D004912:Erythrocytes / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D015017:Yolk Sac / Q000473:pathology
C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C080774:erythroid Kruppel-like factor; D005914:Globins