Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated.
Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated.
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DOI：
10.1186/1471-2164-11-519
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发表时间：
2010-09-27
期刊：
影响因子：
4.4
通讯作者：
Foo RS
中科院分区：
文献类型：
--
作者：
Choy MK;Movassagh M;Goh HG;Bennett MR;Down TA;Foo RS
DNA甲基化可以通过调节DNA与蛋白质或蛋白质复合体之间的相互作用来调节基因的表达。人类基因组中存在保守的共识基序(“预测的转录因子结合位点”：“预测的TFBS”)，但其中绝大多数被染色质免疫沉淀和高通量测序(CHIP-SEQ)证明不是生物转录因子结合位点(“经验TFBS”)。我们假设，在保守的共识基序上的DNA甲基化防止了混乱或无序的转录因子结合。使用人类心脏和精子的全基因组甲基化图谱，我们发现所有保守的共识基序以及位于CpG岛之外的那些基序的子集都具有超甲基化的聚集轮廓。相反，具有保守共识基序的经验性TFBS具有低甲基化的特征。具有保守共识基序的经验性TFBS中有40%位于CpG岛，而所有保守共识基序中只有7%位于CpG岛。最后，我们进一步确定了Tf的少数子集，其特征是在各自保守的共识基序上是低甲基化或中性的，这意味着这些Tf可能负责建立或维持未甲基化的DNA状态，或者其结合不受DNA甲基化的调节。我们的分析支持这样的假设，即至少对于Tf的一个子集，与基因组范围内保守的共识基序的经验结合可能受DNA甲基化控制。
DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
30.8
作者：
Kolasinska-Zwierz P;Down T;Latorre I;Liu T;Liu XS;Ahringer J
通讯作者：
Ahringer J
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M