5-Methylcytosine (5mC) and 5-Hydroxymethylcytosine (5hmC) Enhance the DNA Binding of CREB1 to the C/EBP Half-Site Tetranucleotide GCAA.

5-Methylcytosine (5mC) and 5-Hydroxymethylcytosine (5hmC) Enhance the DNA Binding of CREB1 to the C/EBP Half-Site Tetranucleotide GCAA.
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DOI:
10.1021/acs.biochem.6b00796
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发表时间:
2016-12-13
期刊:
影响因子:
2.9
通讯作者:
Vinson C
Vinson C
中科院分区:
生物学3区
文献类型:
--
作者:
Syed KS;He X;Tillo D;Wang J;Durell SR;Vinson C

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在人类和小鼠干细胞和脑中,5-甲基胞嘧啶(5 mC)和5-羟甲基胞嘧啶(5 hmC)可以出现在CG二核苷酸之外。使用含有60-mer DNA探针的蛋白质结合微阵列(PBMs),我们评估了5 mC和5 hmC对小鼠B-ZIP转录因子(TF)CREB 1,ATF 1和JUND的双链DNA结合的影响。5 mC抑制CREB 1与经典CRE半位点的结合|GTCA但增强与C/EBP半位点的结合|GCAA。5 hmC抑制CREB 1与除TGAT外的所有8聚体的结合|GCAA,其中结合增强。我们观察到类似的DNA结合模式与ATF 1,一个密切相关的B-ZIP域。相反,5 mC和5 hmC均抑制JUND的结合。这些结果鉴定了仅当它们含有5 mC或5 hmC时才被CREB 1和ATF 1良好结合的新DNA序列。两种X射线结构的分析检查了5 mC和5 hmC对CREB和FOS结合DNA的影响|君
In human and mouse stem cells and brain, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) can occur outside of CG dinucleotides. Using protein binding microarrays (PBMs) containing 60-mer DNA probes, we evaluated the effect of 5mC and 5hmC on one DNA strand on the double-stranded DNA binding of the mouse B-ZIP transcription factors (TFs) CREB1, ATF1, and JUND. 5mC inhibited binding of CREB1 to the canonical CRE half-site |GTCA but enhanced binding to the C/EBP half-site |GCAA. 5hmC inhibited binding of CREB1 to all 8-mers except TGAT|GCAA, where binding is enhanced. We observed similar DNA binding patterns with ATF1, a closely related B-ZIP domain. In contrast, both 5mC and 5hmC inhibited binding of JUND. These results identify new DNA sequences that are well-bound by CREB1 and ATF1 only when they contain 5mC or 5hmC. Analysis of two X-ray structures examines the consequences of 5mC and 5hmC on DNA binding by CREB and FOS|JUN.
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