Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.
Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.
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发表时间：
1995
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通讯作者：
M. Greene;B. Blumberg;O. McBride;H. Yi;K. Kronquist;K. Kwan;L. Hsieh;G. Greene;S. Nimer
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作者：
M. Greene;B. Blumberg;O. McBride;H. Yi;K. Kronquist;K. Kwan;L. Hsieh;G. Greene;S. Nimer
转录因子核受体超家族，包括视黄酸受体和 v-erb A，在造血的分子控制中发挥重要作用。为了鉴定造血细胞中表达的核受体，我们使用简并寡核苷酸筛选了人骨髓 cDNA 文库，并分离了编码该超家族新人类成员过氧化物酶体增殖物激活受体 γ (hPPAR γ) 的 1.85 kb 全长 cDNA。两种不同的 hPPAR gamma 转录本在造血细胞中表达：一种 1.85-kb 转录本，对应于全长 mRNA (PPAR gamma 1)，另一种是 0.65-kb 转录本 (PPAR gamma 2)，它不能编码所有核受体功能域。根据 Northern 印迹分析，正常中性粒细胞和外周血淋巴细胞以及 AML、ALL 和 CML 患者的循环白血病细胞仅表达 PPAR gamma 2。相比之下，在多种人类白血病细胞系和培养的正常原代骨髓基质细胞中仅检测到 PPAR gamma 1 转录物。在各种胎儿和成人非造血组织中检测到这两种转录物。我们通过体细胞杂交和连锁分析将 hPPAR gamma 基因定位到人类染色体 3p25。 PPAR 已被证明可被过氧化物酶体增殖剂、长链脂肪酸和花生四烯酸激活。人类 PPAR gamma 虽然与其他物种的 PPAR gamma 同源，但具有独特的序列和氨基酸差异。 hPPAR γ 的鉴定将有助于进一步了解其在人细胞白三烯、前列腺素和过氧化物降解或合成途径中的作用，以及其在脂质代谢和脂肪细胞分化调节中的作用。
The nuclear receptor superfamily of transcription factors, which includes the retinoic acid receptors and v-erb A, play important roles in the molecular control of hematopoiesis. To identify nuclear receptors expressed in hematopoietic cells, we screened a human bone marrow cDNA library using a degenerate oligonucleotide and isolated a 1.85-kb full-length cDNA encoding a new human member of this superfamily, the peroxisome proliferator activated receptor gamma (hPPAR gamma). Two different hPPAR gamma transcripts were expressed in hematopoietic cells: a 1.85-kb transcript, which corresponds to the full-length mRNA (PPAR gamma 1), and a 0.65-kb transcript (PPAR gamma 2), which cannot encode all of the nuclear receptor functional domains. Normal neutrophils and peripheral blood lymphocytes, as well as circulating leukemic cells from patients with AML, ALL, and CML, express only PPAR gamma 2 on Northern blot analysis. In contrast, only the PPAR gamma 1 transcript was detected in a variety of human leukemia cell lines and in cultured normal primary bone marrow stromal cells. Both transcripts were detected in various fetal and adult nonhematopoietic tissues. We mapped the location of the hPPAR gamma gene to human chromosome 3p25 by somatic cell hybridization and linkage analysis. PPARs have been shown to be activated by peroxisome proliferating agents, long-chain fatty acids and arachidonic acid. Human PPAR gamma, although homologous to the PPAR gamma s of other species, has unique sequence and amino acid differences. Identification of hPPAR gamma will allow further understanding of its role in human cellular leukotriene, prostaglandin, and peroxide degradative or synthetic pathways, as well as its role in lipid metabolism and regulation of adipocyte differentiation.