PRIMARY STRUCTURE OF HEPATOCYTE NUCLEAR FACTOR/FORKHEAD HOMOLOG-4 AND CHARACTERIZATION OF GENE-EXPRESSION IN THE DEVELOPING RESPIRATORY AND REPRODUCTIVE EPITHELIUM
PRIMARY STRUCTURE OF HEPATOCYTE NUCLEAR FACTOR/FORKHEAD HOMOLOG-4 AND CHARACTERIZATION OF GENE-EXPRESSION IN THE DEVELOPING RESPIRATORY AND REPRODUCTIVE EPITHELIUM
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DOI：
10.1073/pnas.92.10.4249
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发表时间：
1995-05-09
影响因子：
11.1
通讯作者：
GITLIN, JD
中科院分区：
文献类型：
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作者：
HACKETT, BP;BRODY, SL;GITLIN, JD
有翼螺旋/叉头转录因子家族的成员被认为在细胞特异性基因表达中起作用，从大鼠肺和大鼠睾丸的cDNA文库中分离到一个编码该家族成员的基因，称为肝细胞核因子/叉头同源4(HfH-4)。该基因含有一个由421个氨基酸组成的开放阅读框，含有一个保守的DNA结合区和几个潜在的反式激活区。在小鼠肺发育过程中，在假腺体晚期(胚胎第14.5天)首次准确地检测到一种单一的HfH-4特异性转录本(2.4kb)，并通过原位杂交特异性地定位于近端肺上皮细胞。HfH-4基因在发育中的肺中表达的独特的时空模式决定了该蛋白是启动支气管上皮细胞分化的标志，并提示它在肺发育过程中可能在细胞命运决定中发挥重要作用。除在肺上皮中表达外，RNA印迹分析显示2.4kb的HfH-4在睾丸和输卵管中的转录本。通过使用精子发生遗传缺陷的小鼠，发现HfH-4在睾丸中的表达与单倍体生殖细胞的出现有关，原位杂交研究表明，HfH-4的表达仅限于精子发生的I-W阶段。HfH-4基因在单倍体生殖细胞分化早期的这种表达模式表明，HfH-4可能在调节阶段特异性：肺发育和精子发生过程中的基因表达和细胞命运决定中发挥作用。
Members of the winged helix/forkhead family of transcription factors are believed to play a role in cell-specific gene expression, A cDNA encoding a member of this family of proteins, termed hepatocyte nuclear factor/forkhead homologue 4 (HFH-4), has been isolated from rat lung and rat testis cDNA libraries. This cDNA contains an open reading frame of 421 amino acids with a conserved DNA binding domain and several potential transactivating regions, During murine lung development, a single species of HFH-4-specific transcript (2.4 kb long) is first detected precisely at the start of the late pseudoglandular stage (embryonic day 14.5) and, by in situ hybridization, is specifically localized to the proximal pulmonary epithelium. The unique temporal and spatial pattern of HFH-4 gene expression in the developing lung defines this protein as a marker for the initiation of bronchial epithelial cell differentiation and suggests that it may play an important role in cell fate determination during lung development, In addition to expression in the pulmonary epithelium, RNA blot analysis reveals 2.4 kb HFH-4 transcripts in the testis and oviduct, By using mice with genetic defects in spermatogenesis, HFH-4 expression in the testis is found to be associated with the appearance of haploid germ cells and in situ hybridization studies indicate that HFH-4 expression is confined to stages I-W of spermatogenesis, This pattern of HFH-4 gene expression during the early stages of differentiation of haploid germ cells suggests that HFH-4 may play a role in regulating stage-specific: gene expression and cell-fate determination during lung development and in spermatogenesis,