Cross-species comparison of the sequence of the leukaemia inhibitory factor gene and its protein.
Cross-species comparison of the sequence of the leukaemia inhibitory factor gene and its protein.
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DOI：
10.1111/j.1432-1033.1992.tb16601.x
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
Tracy A. Willson;Donald Metcalf;N. Gough
中科院分区：
文献类型：
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作者：
Tracy A. Willson;Donald Metcalf;N. Gough
白血病抑制因子(LIF)是一种多效性生长因子，在成人和胚胎的不同细胞系统中都有活性。许多哺乳动物的LIF基因高度保守。对绵羊和猪的LIF基因进行了克隆、测序，并与先前发表的小鼠和人的LIF基因序列进行了比较。LIF基因的编码区高度保守，而非编码区在很大程度上是非保守的。在大约340bp的区域，翻译起始密码子的5‘端高度保守(84%)。该区域包括四个保守的TATA盒，两个在小鼠基因中确定的转录起始点，以及作为LIF启动子发挥作用所需的最小区域。然而，与这个高度保守的区域相邻的小鼠基因中似乎包含负控制元件的序列在四个物种之间的保守性很差，除了一个16个保守的核苷酸序列。在大部分非保守的第一内含子中，有一个约150个核苷酸的区块，在所有四个物种之间高度保守(约72%)。然而，小鼠LIF基因内含子1的序列对应于假定的变异型LIF转录本的另一个外显子，物种之间的保守性很差，只有该外显子的残留物在其他三个物种中明显存在。对现有的5种LIF蛋白序列(小鼠、大鼠、人、绵羊和猪)的比较表明，该蛋白具有高度的相似性，从小鼠和绵羊的74%到大鼠和小鼠的92%不等。鉴定了几大块绝对保守的氨基酸序列。对绵羊LIF基因进行了修饰，允许在酵母细胞中生产重组绵羊LIF，该重组绵羊LIF在小鼠细胞上具有生物学活性。
Leukaemia inhibitory factor (LIF) is a pleiotropic growth factor active in diverse cell systems in both the adult and the embryo. The LIF gene from a number of mammalian species is highly conserved. The ovine and porcine LIF genes were cloned, sequenced and compared to the previously published murine and human LIF gene sequences. While the coding regions of the LIF gene are highly conserved, the non-coding regions are largely non-conserved. In a region of approximately 340 bp, the 5' end of the translational initiation codon is highly conserved (84%). This region includes four conserved TATA boxes, two transcriptional start-sites identified in the murine gene and the minimal region required to function as the LIF promoter. A sequence in the murine gene adjacent to this highly conserved region which appears to contain a negative control element is, however, poorly conserved between the four species compared, except for a sequence of 16 conserved nucleotides. Within the largely non-conserved first intron, there is a block of approximately 150 nucleotides which is highly conserved between all four species (approximately 72%). However, a sequence in intron 1 of the murine LIF gene which corresponds to an alternative exon of a putative variant LIF transcript is very poorly conserved between species, with only relics of this exon evident in the other three species. A comparison of the five LIF protein sequences available (murine, rat, human, ovine and porcine) revealed that the protein displays a high degree of similarity, ranging from 74% between mouse and sheep to 92% between rat and mouse. Several large blocks of absolutely conserved amino acid sequence were identified. The ovine LIF gene was modified to allow production of recombinant ovine LIF in yeast cells, which was shown to be biologically active on murine cells.