Chaudhry A Z, Lyons G E, Gronostajski R M
Department of Cancer Biology, Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
Dev Dyn. 1997 Mar;208(3):313-25. doi: 10.1002/(SICI)1097-0177(199703)208:3<313::AID-AJA3>3.0.CO;2-L.
The nuclear factor I (NFI) family of site-specific DNA-binding proteins is required for both the cell-type specific transcription of many viral and cellular genes and for the replication of adenovirus DNA. Although binding sites for NFI proteins within the promoters of several tissue-specific genes have been shown to be essential for their expression, it is unclear which NFI gene products function in specific tissues during development. We have isolated cDNAs from all four murine NFI genes (gene designations Nfia, Nfib, Nfic, and Nfix), assessed the embryonic and postnatal expression patterns of the NFI genes, and determined 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, heart, and other tissues but only weakly expressed in spleen and testis. The embryonic expression patterns of the NFI genes is complex, with NFI-A transcripts appearing earliest-within 9 days postcoitum in the heart and developing brain. The four genes exhibit unique but overlapping patterns of expression during embryonic development, with high level expression of NFI-A, NFI-B, and NFI-X transcripts in neocortex and extensive expression of the four genes in muscle, connective tissue, liver, and other organ systems. The four NFI gene products studied differ in their ability to activate expression of the NFI-dependent MMTV promoter, 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 developmental expression patterns of known NFI-responsive genes. The differential activation of an NFI-dependent promoter, together with the expression 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.
位点特异性DNA结合蛋白的核因子I（NFI）家族对于许多病毒和细胞基因的细胞类型特异性转录以及腺病毒DNA的复制都是必需的。尽管已证明几种组织特异性基因启动子内的NFI蛋白结合位点对其表达至关重要，但尚不清楚在发育过程中哪些NFI基因产物在特定组织中发挥作用。我们从所有四个小鼠NFI基因（基因命名为Nfia、Nfib、Nfic和Nfix）中分离出cDNA，评估了NFI基因的胚胎期和出生后表达模式，并确定了特定NFI蛋白激活NFI依赖性小鼠乳腺肿瘤病毒（MMTV）启动子转录的能力。在成年小鼠中，所有四个NFI基因在肺、肝、心脏和其他组织中表达最高，但在脾脏和睾丸中表达较弱。NFI基因的胚胎表达模式很复杂，NFI-A转录本最早出现——在交配后9天内在心脏和发育中的大脑中出现。这四个基因在胚胎发育过程中表现出独特但重叠的表达模式，NFI-A、NFI-B和NFI-X转录本在新皮层中高水平表达，四个基因在肌肉、结缔组织、肝脏和其他器官系统中广泛表达。所研究的四种NFI基因产物在激活NFI依赖性MMTV启动子表达的能力上有所不同，其中NFI-B蛋白活性最高，NFI-A蛋白活性最低。这些数据在已知NFI反应性基因的发育表达模式的背景下进行了讨论。NFI依赖性启动子的差异激活以及四个基因的表达模式表明，NFI蛋白可能在调节哺乳动物胚胎发育过程中的组织特异性基因表达方面发挥重要作用。
