The organization, promoter analysis, and expression of the human PPAR gamma gene
The organization, promoter analysis, and expression of the human PPAR gamma gene
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DOI：
10.1074/jbc.272.30.18779
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发表时间：
1997-07-25
影响因子：
4.8
通讯作者：
Auwerx, J
中科院分区：
文献类型：
--
作者：
Fajas, L;Auboeuf, D;Auwerx, J
PPAR γ是核受体的PPAR亚家族的成员。在这项工作中，人过氧化物酶体增殖物激活受体γ cDNA和基因的结构进行了测定，其启动子和组织特异性表达的功能进行了表征。与小鼠相似，在人中检测到两种过氧化物酶体增殖体在分析的所有组织中，PPAR γ 2的丰度远低于PPAR γ 1。脂肪组织和大肠中的PPAR γ mRNA水平最高;肾脏、肝脏和小肠中的水平居中;而肌肉中的PPAR γ几乎检测不到。考虑到脂肪酸和花生四烯酸衍生物在结肠疾病中的作用，结肠中PPAR γ的这种高水平表达值得进一步研究。与小鼠PPAR γ类似，人PPAR γ被噻唑烷二酮和前列腺素J激活，并以高亲和力结合PPRE。人类PPAR γ基因有9个外显子，并延伸超过100个基因组DNA的酶。选择性转录起始位点和选择性剪接产生了6 '末端不同的PPAR γ 1和PPAR γ 2 mRNA。PPARgamma 1由8个外显子编码，PPARgamma 2由7个外显子编码。PPAR γ 1的5 '-非翻译序列由外显子A1和A2组成，而PPAR γ 2的5'-非翻译序列加上额外的PPAR γ 2特异性N-末端氨基酸由位于外显子A2和A1之间的外显子B编码。其余6个外显子，称为1至6，是共同的过氧化物酶体增殖物激活受体γ 1和γ 2。基因结构的知识将允许在患有代谢紊乱的人类中筛选PPAR γ突变，而其表达模式和调节其表达的因子的知识在理解其生物学方面可能具有重要意义。
PPAR gamma is a member of the PPAR subfamily of nuclear receptors. In this work, the structure of the human PPAR gamma cDNA and gene was determined, and its promoters and tissue-specific expression were functionally characterized. Similar to the mouse, two PPAR isoforms, PPAR gamma 1 and PPAR gamma 2, were detected in man. The relative expression of human PPAR gamma was studied by a newly developed and sensitive reverse transcriptase-competitive polymerase chain reaction method, which allowed us to distinguish between PPAR gamma 1 and gamma 2 mRNA. In all tissues analyzed, PPAR gamma 2 was much less abundant than PPAR gamma 1. Adipose tissue and large intestine have the highest levels of PPAR gamma mRNA; kidney, liver, and small intestine have intermediate levels; whereas PPAR gamma is barely detectable in muscle. This high level expression of PPAR gamma in colon warrants further study in view of the well established role of fatty acid and arachidonic acid derivatives in colonic disease. Similarly as mouse PPAR gamma s, the human PPAR gamma s are activated by thiazolidinediones and prostaglandin J and bind with high affinity to a PPRE. The human PPAR gamma gene has nine exons and extends over more than 100 kilobases of genomic DNA. Alternate transcription start sites and alternate splicing generate the PPAR gamma 1 and PPAR gamma 2 mRNAs, which differ at their 6'-ends. PPAR gamma 1 is encoded by eight exons, and PPAR gamma 2 is encoded by seven exons. The 5'-untranslated sequence of PPAR gamma 1 is comprised of exons A1 and A2, whereas that of PPAR gamma 2 plus the additional PPAR gamma 2-specific N-terminal amino acids are encoded by exon B, located between exons A2 and A1. The remaining six exons, termed 1 to 6, are common to the PPAR gamma 1 and gamma 2. Knowledge of the gene structure will allow screening for PPAR gamma mutations in humans with metabolic disorders, whereas knowledge of its expression pattern and factors regulating its expression could be of major importance in understanding its biology.