Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family
Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family
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DOI：
10.1101/gad.1561707
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发表时间：
2007-08-01
影响因子：
10.5
通讯作者：
Graves, Barbara J.
中科院分区：
文献类型：
--
作者：
Hollenhorst, Peter C.;Shah, Atul A.;Graves, Barbara J.
转录因子家族中体外DNA结合特性的保守性对实现体内特异性提出了挑战。为了揭示ETS基因家族内调节特异性的机制，我们使用染色质免疫沉淀结合全基因组启动子微阵列来查询人类T细胞系中三种ETS蛋白的占用率。出乎意料的是，经常检测到冗余占用，而特定占用的可能性较小。冗余结合与管家类基因，而具体的结合的例子代表更专门的基因。生物信息学方法表明，冗余结合与转录起始位点附近的共识ETS结合序列相关。与此相反，特异性结合位点显着偏离共识，并发现进一步从转录起始位点。一个途径特异性被发现-一个高度分散的结合位点，促进ETS 1和RUNX 1的合作DNA结合。特异性和冗余的DNA结合模式表明ETS转录因子家族成员有两种不同的作用。
The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within the ETS gene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found-a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family.