Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells
Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells
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DOI：
10.1074/jbc.271.38.23126
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发表时间：
1996-09-20
影响因子：
4.8
通讯作者：
Hromas, R
中科院分区：
文献类型：
--
作者：
Sutton, J;Costa, R;Hromas, R
有翼螺旋（原HNF-3/叉头）转录调控家族的一个新成员，被称为Genesis，被分离和表征。对完整cDNA的推测翻译表明，翼状螺旋DNA结合域位于蛋白质的中心位置，两侧的区域包含已知的转录调控基序。Northern对Genesis的广泛分析发现，该信息仅在胚胎干细胞或其恶性等同物胚胎癌细胞中表达。当这些细胞被刺激分化时，Genesis转录本被下调。对Genesis蛋白与之相互作用的DNA序列进行了表征，并发现其包含与胚胎干细胞增强子序列相似的共识，go转染实验揭示了Genesis是一种转录抑制因子。Genesis定位于小鼠4号染色体上与人类染色体1p31相同的区域，这是生殖细胞瘤、神经母细胞瘤和急性淋巴细胞白血病的非随机异常位点，是调节正常或恶性胚胎干细胞表型的候选基因。
A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized. Putative translation of the complete cDNA revealed the winged helix DNA binding domain to be centrally located within the protein, with regions on either side that contain known transcriptional regulatory motifs. Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells. The Genesis transcript was down-regulated when these cells were stimulated to differentiate. DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence, Go-transfection experiments revealed that Genesis is a transcriptional repressor. Genesis mapped to mouse chromosome 4 in a region syntenic with human chromosome 1p31, a site of nonrandom abnormalities in germ cell neoplasia, neuroblastoma, and acute lymphoblastic leukemia, Genesis is a candidate for regulating the phenotype of normal or malignant embryonic stem cells.