CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.
CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.
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DOI：
10.1093/nar/gkt910
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Bartolomei MS
中科院分区：
文献类型：
--
作者：
Plasschaert RN;Vigneau S;Tempera I;Gupta R;Maksimoska J;Everett L;Davuluri R;Mamorstein R;Lieberman PM;Schultz D;Hannenhalli S;Bartolomei MS
CTCF（CCCTC-结合因子）是一种高度保守的多功能DNA结合蛋白，在全基因组范围内具有数千个结合位点。我们以前的工作表明，CTCF的结合位点序列的差异可能会影响CTCF的募集和功能的调节。为了研究这种可能性，我们表征了小鼠胚胎干细胞分化过程中全基因组CTCF结合和基因表达的变化。基于与共有基序的相似性将CTCF位点分为三类（LowOc，MedOc和HighOc）后，我们发现发育调节的CTCF结合优先发生在LowOc位点，其与共有基序的相似性较低。通过测量CTCF对选定位点的亲和力，我们发现分化过程中丢失的位点富含与体外较弱CTCF结合相关的基序。具体而言，在CTCF结合位点的第18位富集T与LowOc类中的调节结合相关，并且可以预测地降低CTCF对结合位点的亲和力。最后，通过比较CTCF结合的变化与分化过程中基因表达的变化，我们发现LowOc和HighOc位点与不同的调控功能相关。我们的研究结果表明，CTCF的调控部分依赖于其结合位点内的特定基序。
CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF’s binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18th position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
64.8
作者：
Hark, AT;Schoenherr, CJ;Tilghman, SM
通讯作者：
Tilghman, SM
影响因子：
7
作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
12.3
作者：
Essien K;Vigneau S;Apreleva S;Singh LN;Bartolomei MS;Hannenhalli S
通讯作者：
Hannenhalli S