ORGANIZATION, INDUCIBLE-EXPRESSION AND CHROMOSOME LOCALIZATION OF THE HUMAN HMG-I(Y) NONHISTONE PROTEIN GENE
ORGANIZATION, INDUCIBLE-EXPRESSION AND CHROMOSOME LOCALIZATION OF THE HUMAN HMG-I(Y) NONHISTONE PROTEIN GENE
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DOI：
10.1093/nar/21.18.4259
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发表时间：
1993-09-11
影响因子：
14.9
通讯作者：
REEVES, R
中科院分区：
文献类型：
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作者：
FRIEDMANN, M;HOLTH, LT;REEVES, R
哺乳动物非组蛋白HMG-I（Y）家族成员具有重要意义，因为它们已被证明特异性结合A的小沟。体外和体内富含T的序列，并在体内充当基因转录调节蛋白。本文报道了人HMG-Ⅰ（Y）基因的克隆、测序、鉴定和染色体定位。该基因具有几个潜在的启动子/增强子区域，许多不同的转录起始位点和许多可变剪接的外显子，使其成为迄今为止报道的最复杂的非组蛋白染色质蛋白编码基因之一。推定的启动子/增强子区各自含有许多保守的核苷酸序列，用于潜在地结合诱导型调节转录因子。与这些保守序列的存在相一致，我们发现HMG-I（Y）基因的转录在人类淋巴细胞中可被佛波醇酯和钙离子载体等因子诱导。详细的序列分析证实了我们先前的建议，即前体mRNA的选择性剪接产生了在人类细胞中发现的主要HMG-I和HMG-Y同种型蛋白。此外，该基因的外显子-内含子排列完全解释了所有先前克隆的人HMG-I（Y）cDNA（1，2）。同样令人感兴趣的是，存在于单个HMG-I（Y）蛋白中的三种不同的DNA结合结构域肽中的每一种都由存在于单独外显子上的序列编码，因此可能允许这些功能结构域在进化过程中进行外显子“改组”。最后，我们将该基因定位于6号染色体的短臂（6p），该区域已知与重排，易位和其他与许多人类癌症相关的异常有关。
Members of the HMG-I(Y) family of mammalian nonhistone proteins are of importance because they have been demonstrated to bind specifically to the minor groove of A . T-rich sequences both in vitro and in vivo and to function as gene transcriptional regulatory proteins in vivo. Here we report the cloning, sequencing, characterization and chromosomal localization of the human HMG-I(Y) gene. The gene has several potential promoter/enhancer regions, a number of different transcription start sites and numerous alternatively spliced exons making it one of the most complex nonhistone chromatin protein-encoding genes so far reported. The putative promoter/enhancer regions each contain a number of conserved nucleotide sequences for potential binding of inducible regulatory transcription factors. Consistent with the presence of these conserved sequences, we found that transcription of the HMG-I(Y) gene is inducible in human lymphoid cells by factors such as phorbol esters and calcium ionophores. Detailed sequence analysis confirms our earlier suggestion that alternative splicing of precursor mRNAs gives rise to the major HMG-I and HMG-Y isoform proteins found in human cells. Furthermore, the gene's exon-intron arrangement fully accounts for all of the previously cloned human HMG-I(Y) cDNAs (1,2). Also of considerable interest is the fact that each of the three different DNA-binding domain peptides present in an individual HMG-I(Y) protein is coded for by sequences present on separate exons thus potentially allowing for exon 'shuffling' of these functional domains during evolution. And, finally, we localized the gene to the short arm of chromosome 6 (6p) in a region that is known to be involved in rearrangements, translocations and other abnormalities correlated with a number of human cancers.