EXPRESSION PATTERNS OF THE 4 NUCLEAR FACTOR-I GENES DURING MOUSE EMBRYOGENESIS INDICATE A POTENTIAL ROLE IN DEVELOPMENT

The nuclear factor I (NFI) family of site-specific DNA-binding protein s is required for both the cell-type specific transcription of many vi ral and cellular genes and for the replication of adenovirus DNA, Alth ough binding sites for NFI proteins within the promoters of several ti ssue-specific genes have been shown to be essential for their expressi on, it is unclear which NFI gene products function in specific tissues during development, We have isolated cDNAs from all four murine NFI g enes (gene designations Nfia, Nfib, Nfic, and Nfix), assessed the embr yonic and postnatal expression patterns of the NFI genes, and determin ed the ability of specific NFI proteins to activate transcription from the NFI-dependent mouse mammary tumor virus (MMTV) promoter, In adult mice, all four NFI genes are most highly expressed in lung, liver, he art, and other tissues but only weakly expressed in spleen and testis, The embryonic expression patterns of the NFI genes is complex, with N FI-A transcripts appearing earliest-within 9 days postcoitum in the he art and developing brain, The four genes exhibit unique but over-lappi ng patterns of expression during embryonic development, with high leve l expression of NFI-A, NFI-B, and NFI-X transcripts in neocortex and e xtensive expression of the four genes in muscle, connective tissue, li ver, and other organ systems, The four NFI gene products studied diffe r in their ability to activate expression of the NFI-dependent MMTV pr omoter, with the NFI-B protein being most active and the NFI-A protein being least active, These data are discussed in the context of the de velopmental expression patterns of known NFI-responsive genes, The dif ferential activation of an NFI-dependent promoter, together with the e xpression patterns observed for the four genes, indicate that the NFI proteins may play an important role in regulating tissue-specific gene expression during mammalian embryogenesis. (C) 1997 Wiley-Liss, Inc.