A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation.
A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation.
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羟甲基胞嘧啶和甲酰胞嘧啶结合蛋白的筛选表明其在转录和染色质调节中的功能。
DOI：
10.1186/gb-2013-14-10-r119
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Reik W
中科院分区：
文献类型：
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作者：
Iurlaro M;Ficz G;Oxley D;Raiber EA;Bachman M;Booth MJ;Andrews S;Balasubramanian S;Reik W
DNA甲基化(5mC)在基因组功能的表观遗传调控中起着重要作用。最近发现，Tet羟基酶可以将DNA中的5mC氧化成羟甲基胞嘧啶(5hmC)、甲酰胞嘧啶(5fC)和羧基胞嘧啶(5caC)。这些衍生物在DNA去甲基化中发挥作用，但除此之外，它们本身也可能具有表观遗传信号功能。最近的一项研究发现了优先与5-甲基胞嘧啶(5mC)及其氧化形式结合的蛋白质，其中5mC和5hmC的读数几乎没有重叠，与进一步氧化形式结合的蛋白质富含修复蛋白和转录调节因子。我们通过使用启动子序列作为诱饵来扩展这项研究，并使用小鼠胚胎干细胞提取液中的DNA将蛋白质结合模式与未修饰或修饰的胞嘧啶进行比较。我们比较了两个具有不同CpG组成的DNA探针的蛋白质富集率，结果表明，尽管一些富集物对胞嘧啶修饰具有特异性，但另一些富集物对修饰和靶序列都是选择性的。只有少数蛋白质偏好5hmC(如RPL26、Prp8和DNA错配修复蛋白MHS6)，但偏好5fC的蛋白质更多，包括转录调节因子(FOXK1、FOXK2、Foxp1、FOXP4和foxI3)、DNA修复因子(TDG和MPG)和染色质调节因子(EHMT1、L3MBTL2和NuRD复合体的所有成分)。Our Screen已经在具有不同CpG组成的基因组序列中发现了与5fc结合的新蛋白，并表明它们调节转录和染色质，从而开启了5fc阅读器的功能研究。
DNA methylation (5mC) plays important roles in epigenetic regulation of genome function. Recently, TET hydroxylases have been found to oxidise 5mC to hydroxymethylcytosine (5hmC), formylcytosine (5fC) and carboxylcytosine (5caC) in DNA. These derivatives have a role in demethylation of DNA but in addition may have epigenetic signaling functions in their own right. A recent study identified proteins which showed preferential binding to 5-methylcytosine (5mC) and its oxidised forms, where readers for 5mC and 5hmC showed little overlap, and proteins bound to further oxidation forms were enriched for repair proteins and transcription regulators. We extend this study by using promoter sequences as baits and compare protein binding patterns to unmodified or modified cytosine using DNA from mouse embryonic stem cell extracts. We compared protein enrichments from two DNA probes with different CpG composition and show that, whereas some of the enriched proteins show specificity to cytosine modifications, others are selective for both modification and target sequences. Only a few proteins were identified with a preference for 5hmC (such as RPL26, PRP8 and the DNA mismatch repair protein MHS6), but proteins with a strong preference for 5fC were more numerous, including transcriptional regulators (FOXK1, FOXK2, FOXP1, FOXP4 and FOXI3), DNA repair factors (TDG and MPG) and chromatin regulators (EHMT1, L3MBTL2 and all components of the NuRD complex). 0ur screen has identified novel proteins that bind to 5fC in genomic sequences with different CpG composition and suggests they regulate transcription and chromatin, hence opening up functional investigations of 5fC readers.
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影响因子：
14.9
作者：
Hashimoto H;Zhang X;Cheng X
通讯作者：
Cheng X
影响因子：
2.7
作者：
NOCE, T;FUJIWARA, Y;HIGASHINAKAGAWA, T
通讯作者：
HIGASHINAKAGAWA, T
影响因子：
2.7
作者：
Fujii, Yoshito;Nakamura, Michio
通讯作者：
Nakamura, Michio
影响因子：
14.9
作者：
Jin SG;Wu X;Li AX;Pfeifer GP
通讯作者：
Pfeifer GP
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
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作者：
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