The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation
The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation
复制标题
DOI：
10.1093/nar/26.22.5163
复制
发表时间：
1998-11-15
影响因子：
14.9
通讯作者：
Turker, MS
中科院分区：
文献类型：
--
作者：
Mummaneni, P;Yates, P;Turker, MS
小鼠腺嘌呤磷酸核糖转移酶（aprt）基因的启动子区在其5'端含有一个非共有Spl结合位点，随后是三个共有Spl结合位点。两个最3 '结合位点足以使aprt最大化表达，表明5'端的非共有和共有结合位点是冗余的。然而，两个3'位点不足以阻断表观遗传失活，这导致需要冗余的共有和/或非共有5' Spl结合位点来阻断失活事件的假设。为了检验该假设，制备启动子区构建体，其中两个5 ′ Sp1结合位点单独或串联突变，然后测试每个构建体承受表观遗传失活的能力。通常位于启动子上游1.2kb的顺式作用甲基化中心用于诱导失活，结果表明，需要存在冗余的共有Spl结合位点来阻断甲基化相关的基因失活。因此，包含小鼠aprt启动子的Spl结合位点已经进化出两种不同的功能，一个促进转录，另一个阻断表观遗传失活。
The promoter region of the mouse adenine phosphoribosyltransferase (aprt) gene contains one nonconsensus Spl binding site at its 5' end followed by three consensus Spl binding sites. The two 3'-most binding sites are sufficient for maximal expression of aprt, suggesting that the non-consensus and consensus binding sites at the 5' end are redundant, However, the two 3' sites are not sufficient to block epigenetic inactivation, which led to the hypothesis that the redundant consensus and/or non-consensus 5' Spl binding sites are required to block inactivation events, To test this hypothesis, promoter region constructs were made in which the two 5' Spl binding sites were mutated alone or in tandem, and then each construct was tested for its ability to withstand epigenetic inactivation, A cis-acting methylation center that is normally located 1.2 kb upstream of the promoter was used to induce inactivation, The results demonstrate that the presence of the redundant consensus Spl binding site is required to block methylation-associated gene inactivation, Therefore, the Spl binding sites comprising the mouse aprt promoter have evolved two distinct functions, one to promote transcription and the other to block epigenetic inactivation.