Embryonic lethality, decreased erythropoiesis, and defective octamer-dependent promoter activation in Oct-1-deficient mice.
Oct-1 is a sequence-specific DNA binding transcription factor that is believed to regulate a large group of tissue-specific and ubiquitous genes. Both Oct-1 and the related but tissue-restricted Oct-2 protein bind to a DNA sequence termed the octamer motif (5'-ATGCAAAT-3') with equal affinity in vitro. To address the role of Oct-1 in vivo, an Oct-1-deficient mouse strain was generated by gene targeting. Oct-1-deficient embryos died during gestation, frequently appeared anemic, and suffered from a lack of Ter-119-positive erythroid precursor cells. This defect was cell intrinsic. Fibroblasts derived from these embryos displayed a dramatic decrease in Oct-1 DNA binding activity and a lack of octamer-dependent promoter activity in transient transfection assays. Interestingly, several endogenous genes thought to be regulated by Oct-1 showed no change in expression. When crossed to Oct-2(+/-) animals, transheterozygotes were recovered at a very low frequency. These findings suggest a critical role for Oct-1 during development and a stringent gene dosage effect with Oct-2 in mediating postnatal survival.
Wang
Victoria E H
VE
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, USA.
Schmidt
Tara
T
Chen
Jianzhu
J
Sharp
Phillip A
PA
Tantin
Dean
D
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020964:Embryo Loss / Q000235:genetics*; D004920:Erythropoiesis / Q000235:genetics* / Q000502:physiology; D018390:Gene Targeting; D005804:Genes, Lethal; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006579:Heterozygote; D051863:Host Cell Factor C1; D051379:Mice; D009154:Mutation; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors; D005914:Globins