期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 24, 期 3, 页码 1022-1032出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.3.1022-1032.2004
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资金
- NCI NIH HHS [P30 CA014051, P01-CA42063, P01 CA042063, P30-CA14051] Funding Source: Medline
- PHS HHS [A140416] Funding Source: Medline
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.
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