ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes.
ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes.
复制标题
DOI：
10.1186/1756-8935-6-13
复制
发表时间：
2013-05-21
影响因子：
3.9
通讯作者：
Farnham PJ
中科院分区：
文献类型：
--
作者：
Blattler A;Yao L;Wang Y;Ye Z;Jin VX;Farnham PJ
DNA甲基化和抑制性组蛋白修饰协同沉默启动子。甲基化DNA区域获得抑制性组蛋白修饰的一种机制是通过甲基DNA结合转录因子。锌指蛋白ZBTB 33（也称为Kaiso）已在体外显示优先结合甲基化DNA，并与SMRT/NCoR组蛋白脱乙酰酶复合物相互作用。我们对Kaiso ChIP-seq和DNA甲基化数据集进行了生物信息学分析，以测试Kaiso与甲基化CpG的结合导致靶启动子处乙酰化组蛋白丢失的模型。我们的研究结果表明，与预期相反，Kaiso在体内不与甲基化DNA结合，而是与标记有高水平乙酰化组蛋白的高活性启动子结合。此外，我们的研究表明，DNA甲基化和核小体占据模式限制Kaiso进入潜在的结合位点，并影响细胞类型特异性结合。我们提出了一个新的模型，全基因组的结合和功能的Kaiso，Kaiso结合到未甲基化的调控区，并有助于目标启动子的活性状态。
DNA methylation and repressive histone modifications cooperate to silence promoters. One mechanism by which regions of methylated DNA could acquire repressive histone modifications is via methyl DNA-binding transcription factors. The zinc finger protein ZBTB33 (also known as Kaiso) has been shown in vitro to bind preferentially to methylated DNA and to interact with the SMRT/NCoR histone deacetylase complexes. We have performed bioinformatic analyses of Kaiso ChIP-seq and DNA methylation datasets to test a model whereby binding of Kaiso to methylated CpGs leads to loss of acetylated histones at target promoters. Our results suggest that, contrary to expectations, Kaiso does not bind to methylated DNA in vivo but instead binds to highly active promoters that are marked with high levels of acetylated histones. In addition, our studies suggest that DNA methylation and nucleosome occupancy patterns restrict access of Kaiso to potential binding sites and influence cell type-specific binding. We propose a new model for the genome-wide binding and function of Kaiso whereby Kaiso binds to unmethylated regulatory regions and contributes to the active state of target promoters.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btq669
发表时间：
2011-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lan X;Bonneville R;Apostolos J;Wu W;Jin VX
通讯作者：
Jin VX
影响因子：
14.9
作者：
Blahnik KR;Dou L;O'Geen H;McPhillips T;Xu X;Cao AR;Iyengar S;Nicolet CM;Ludäscher B;Korf I;Farnham PJ
通讯作者：
Farnham PJ
影响因子：
3.5
作者：
Buck-Koehntop BA;Martinez-Yamout MA;Dyson HJ;Wright PE
通讯作者：
Wright PE
影响因子：
13.8
作者：
Liu, Yiwei;Zhang, Xing;Blumenthal, Robert M.;Cheng, Xiaodong
通讯作者：
Cheng, Xiaodong
影响因子：
7
作者：
Kelly TK;Liu Y;Lay FD;Liang G;Berman BP;Jones PA
通讯作者：
Jones PA