CTCF
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转录阻抑物CTCF,也被称为11锌指蛋白或CCCTC结合因子,是由人类CTCF基因编码的转录因子[1][2]。CTCF参与多个细胞进程,包括转录调控、绝缘子活性调控、V(D)J重组、染色质结构调控等[3][4]。
发现
CTCF最早被认为在鸡体内抑制c-myc基因表达。CTCF蛋白和以CCCTC为核心序列的三个规则间隔重复蛋白相结合,故得名CCCTC结合因子[5]。
功能
CTCF的主要功能是调控染色质的3D结构[4]。CTCF和DNA双链结合形成染色质环,并把DNA锚定在细胞结构上(例如核纤层)[6]。此外,CTCF还能充当常染色质和异染色质的边界。
DNA的3D结构会影响基因的调控,因此CTCF的活性会影响基因表达。绝缘子能阻碍增强子和启动子的结合,而CTCF是绝缘子的主要活性部分[5]。
已观测到的活性
CTCF的结合有多种效应。目前尚不能确定下列功能是直接由CTCF导致。
转录调控
CTCF对于IGF2的抑制起重要作用。具体机制为CTCF和H19基因的基因铭印(ICR)区域、差异甲基化区域-1(DMR-1)和MAR3区域结合[7]。
绝缘子
CTCF能通过和目标区域结合以阻碍增强子和启动子的相互作用,从而降低增强子对某些功能域的调控能力[8]。除此之外,CTCF还能作为染色质“路障”,阻止异染色质的进一步形成。
染色质结构调控
CTCF往往以二聚体的形式存在,这会导致DNA形成环状结构。CTCF也经常在DNA和核纤层的结合处出现。使用ChIP-seq技术可以发现CTCF同黏连蛋白一起在基因组内广泛存在,并对染色质的高级结构起调节作用[9][10][11]。
RNA剪切调控
CTCF对mRNA剪切有调控作用[12]。
与DNA结合
CTCF和共有序列CCGCGNGGNGGCAG相结合。这条序列在其结构域中有11个锌指结构。CTCF和基因的结合被CpG的甲基化所影响[13][14]。
CTCF在19个细胞系中大约有55000个共同的DNA结合位点(共77811个独特位点)。CTCF能和不同的锌指结构结合,这让它的功能非常多样化。大约有30000个CTCF的位点功能已经被定义。在人类的不同细胞中大约有15000-40000个CTCF结合位点。除此之外,高分辨率的核小体比对现实CTCF的不同结合位点可能和核小体的定位有关[15][16][17][18]。
蛋白互作
CTCF可能和Y box结合蛋白1有相互作用[19]。黏连蛋白对CTCF形成的环状结构有稳定作用[20]。
参考
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衍生阅读
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