Activating transcription factor 1 and CREB are important for cell survival during early mouse development.
Activating transcription factor 1 (ATF1), CREB, and the cyclic AMP (cAMP) response element modulatory protein (CREM), which constitute a subfamily of the basic leucine zipper transcription factors, activate gene expression by binding as homo- or heterodimers to the cAMP response element in regulatory regions of target genes. To investigate the function of ATF1 in vivo, we inactivated the corresponding gene by homologous recombination. In contrast to CREB-deficient mice, which suffer from perinatal lethality, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities. Since ATF1 and CREB but not CREM are strongly coexpressed during early mouse development, we generated mice deficient for both CREB and ATF1. ATF1(-/-) CREB(-/-) embryos die before implantation due to developmental arrest. ATF1(+/-) CREB(-/-) embryos display a phenotype of embryonic lethality around embryonic day 9.5 due to massive apoptosis. These results indicate that CREB and ATF1 act in concert to mediate signals essential for maintaining cell viability during early embryonic development.
Bleckmann
Susanne C
SC
Department of Molecular Biology of the Cell I, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Blendy
Julie A
JA
Rudolph
Dorothea
D
Monaghan
A Paula
AP
Schmid
Wolfgang
W
Schütz
Günther
G
D051697:Activating Transcription Factor 1; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D020964:Embryo Loss / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors