YY1 and Sp1 transcription factors bind the human transferrin gene in an age-related manner
YY1 and Sp1 transcription factors bind the human transferrin gene in an age-related manner
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DOI：
10.1093/gerona/51a.1.b66
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发表时间：
1996-01-01
影响因子：
5.1
通讯作者：
Bowman, BH
中科院分区：
文献类型：
--
作者：
Adrian, GS;Seto, E;Bowman, BH
铁结合蛋白转铁蛋白在运输、递送和螯合由身体组织获得的铁离子中具有主要作用。然而，在衰老过程中，人类血清转铁蛋白水平下降。同样，在携带嵌合人转铁蛋白转基因的转基因小鼠中，转铁蛋白转基因的肝脏表达随年龄而降低。衰老调节是由于基因转录减少。电泳迁移率变动分析和抗体识别已经揭示了人转铁蛋白基因的5'调节元件与三种YY 1蛋白质（称为YY 1、YY 1-a和YY 1-B）和Sp1-a转录因子的结合。YY 1-a和YY 1-B结合活性随年龄增加而增加，Sp1样结合活性随年龄降低而降低。由于Sp1是一个正转录因子，而YY 1可能是一个负转录因子，它们与年龄结合的改变可能导致人转铁蛋白转基因转录的降低，以及与年龄相关的人血清转铁蛋白水平的降低。
The iron-binding protein transferrin has major roles in transporting, delivering, and sequestering ferric ions acquired by body tissues. Yet, during aging, serum transferrin levels decrease in humans. Likewise, in transgenic mice carrying chimeric human transferrin transgenes, liver expression of transferrin transgenes decreases with age. The aging regulation is due to decreased gene transcription. Electrophoretic mobility shift assays and antibody-recognition have revealed the binding of 5' regulatory elements of the human transferrin gene by three YY1 proteins, called YY1, YY1-a, and YY1-b, and an Sp1-a transcription factor. An age-related increase in YY1-a and YY1-b binding activities and a decrease in Sp1-like binding activity were shown. Since Sp1 is a positive transcription factor and YY1 can be a negative transcription factor, the alterations in their binding with age could cause the decreased transcription of the human transferrin transgene, and also the age-related decreased serum transferrin levels in humans.