CLUSTERED ORGANIZATION OF HOMOLOGOUS KRAB ZINC-FINGER GENES WITH ENHANCED EXPRESSION IN HUMAN T-LYMPHOID CELLS
CLUSTERED ORGANIZATION OF HOMOLOGOUS KRAB ZINC-FINGER GENES WITH ENHANCED EXPRESSION IN HUMAN T-LYMPHOID CELLS
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DOI：
10.1002/j.1460-2075.1993.tb05781.x
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发表时间：
1993-04-01
期刊：
影响因子：
11.4
通讯作者：
MARTIAL, JA
中科院分区：
文献类型：
--
作者：
BELLEFROID, EJ;MARINE, JC;MARTIAL, JA
Krab锌指蛋白(KRAB-ZFP)是Kruppel C2H2型ZFP的一个大亚家族。Krab(Kruppel-Association box)是一个进化上保守的蛋白质结构域，在N端发现，与手指重复序列有关。我们在这里报告了高度相关的人类KRAB-ZFP的一个特殊亚群的特征。ZNF91是这个亚群的代表之一，在其C-末端包含35个连续的RINER重复序列。通过聚合酶链式反应分离到3个与ZNF91序列一致的mRNA异构体。这些编码蛋白具有KRAB结构域，存在、部分缺失或缺失。确定了五个基因组片段，每个片段编码一个基因的一部分：ZNF91基因或四个不同的、相关的KRAB-ZFP基因之一。它们都表现出一个共同的外显子/内含子组织，变异的锌指重复序列组织在一个外显子中，KRAB结构域由两个独立的外显子编码。内含子的这种定位支持这样的假设，即编码KRAB结构域中具有可变性的多肽的mRNA异构体可能通过选择性剪接而产生。通过原位染色体定位研究和对含有KRAB-ZFP基因的人基因组酵母人工染色体文库片段的分析，我们发现这些基因是成簇存在的，特别是在染色体19p12-p13.1区域发现了一个包含40多个基因的基因复合体。这些ZNF91相关基因可能在进化后期才出现，因为在小鼠和大鼠基因组中没有检测到同源基因。虽然这个KRAB-ZFP基因亚群的成员在ATL人类组织中可检测到转录，但它们在人类T淋巴样细胞中的表达显著高于ATL。
KRAB zinc-finger proteins (KRAB-ZFPs) constitute a large subfamily of ZFPs of the Kruppel C2H2 type. KRAB (Kruppel-associated box) is an evolutionarily conserved protein domain found N-terminally with respect to the finger repeats. We report here the characterization of a particular subgroup of highly related human KRAB-ZFPs. ZNF91 is one representative of this subgroup and contains 35 contiguous ringer repeats at its C-terminus. Three mRNA isoforms with sequence identity to ZNF91 were isolated by the polymerase chain reaction. These encode proteins with a KRAB domain present, partially deleted or absent. Five genomic fragments were characterized, each encoding part of a gene: the ZNF91 gene or one of four distinct, related KRAB-ZFP genes. All exhibit a common exon/intron organization with the variant zinc finger repeats organized in a single exon and the KRAB domain encoded by two separate exons. This positioning of introns supports the hypothesis that the mRNA isoforms encoding polypeptides with variability in the KRAB domain could arise by alternative splicing. By in situ chromosomal mapping studies and by analysis of fragments from a human genomic yeast artificial chromosome library containing KRAB-ZFP genes, we show that these genes occur in clusters; in particular, a gene complex containing over 40 genes has been identified in chromosomal region 19p12-p13.1. These ZNF91-related genes probably arose late during evolution since no homologous genes are detected in the mouse and rat genomes. Although the transcription of members of this KRAB-ZFP gene subgroup is detectable in atl human tissues, their expression is significantly higher in human T lymphoid cells.