Focus on molecules: 5-methylcytosine, a possible epigenetic link between ageing and ocular disease.
Focus on molecules: 5-methylcytosine, a possible epigenetic link between ageing and ocular disease.
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关注分子：5-甲基胞嘧啶，衰老与眼部疾病之间可能存在的表观遗传联系。
DOI：
10.1016/j.exer.2010.06.026
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发表时间：
2012
影响因子：
3.4
通讯作者：
Guzman,AlvaroE
中科院分区：
文献类型：
--
作者：
Mitton,KennethP;Guzman,AlvaroE
胞嘧啶甲基化为5-甲基胞嘧啶是一种表观遗传基因调控机制，与所有组织的衰老和疾病有关。更熟悉的基因调控方面涉及转录因子与基因启动子中同源DNA序列的结合。然而，表观遗传机制也在不改变基因组DNA序列的情况下控制基因表达。这个表观基因组实际上是“覆盖在基因组上”。从根本上说，表观遗传调控控制染色质结构，从而影响DNA结合蛋白与DNA的接触。染色质由与核小体核心组蛋白（H2A, H2B, H3, H4）相关的基因组DNA组成。染色质的基本亚基是核小体，由组蛋白八聚体（每个组蛋白两个）组成，DNA绕着它盘绕大约2圈。dna甲基化通过与组蛋白翻译后修饰的串扰改变染色质结构。我们建议读者参考最近对这些和其他与眼睛发育和疾病相关的表观遗传机制的综述（Cvekl和Mitton， 2010）。5-甲基胞嘧啶及其与胞嘧啶、胸腺嘧啶和尿嘧啶的转化如图1A所示。在哺乳动物中，胞嘧啶的甲基化是最常见的CpG二核苷酸（甲基-CpG）。CpG基序两条链上的胞嘧啶被甲基化。在哺乳动物基因组中，CpG二核苷酸的相对频率低于预期，CpG基序在基因启动子区域更为普遍。随着时间的推移，甲基- cpg可能会降解为TpG，除非其基本功能维持了基序。非cpg胞嘧啶的甲基化确实发生，但这种甲基化的程度在大多数组织中尚不清楚。
Methylation of cytosine, to 5-methylcytosine, is an epigenetic gene regulatory mechanism with implications for ageing and disease in all tissues. More familiar aspects of gene regulation concern the binding of transcription factors to their cognate DNA sequences in gene promoters. However, epigenetic mechanisms also control gene expression without altering the genomic DNA sequence. This epigenome is literally “overlaid on the genome”. Fundamentally, epigenetic regulation controls the chromatin architecture to affect the access of DNA binding proteins to the DNA. Chromatin is comprised of genomic DNA associated with the nucleosome core histone proteins (H2A, H2B, H3, H4). The fundamental subunit of chromatin is the nucleosome, comprised of a histone octamer (two of each histone) around which the DNA is coiled for about 2 complete turns. DNA-methylation alters chromatin architecture through cross talk with the post-translational modification of histone proteins. We refer readers to a recent review of these and other epigenetic mechanisms relevant to eye development and disease (Cvekl and Mitton, 2010).5-Methylcytosine and its conversions with cytosine, thymine, and uracil are illustrated in Figure 1A. In mammals, methylation of cytosine is most common at CpG dinucleotides (Methyl-CpG). Cytosines in both strands of the CpG motif are methylated. In the mammalian genome, the relative frequency of CpG dinucleotides is lower than expected, and CpG motifs are more prevalent in gene promoter regions. Methyl-CpG may deaminate to TpG over time, except where essential function maintains the motif. Methylation of non-CpG cytosines does occur, but the extent of this methylation is not yet known for most tissues.
翼状胬肉中 p16 基因启动子的高甲基化及其与 DNA 甲基转移酶 3b 表达的关系。
影响因子：
2.2
作者：
Pei;Ya‐Wen Cheng;Chun;S. Tseng;Pak Sam Chau;Y. Tsai
通讯作者：
Y. Tsai
原发性散发性葡萄膜黑色素瘤中 p16 (CDKN2/MTS-1/INK4A) 改变的分析。
DOI：
--
发表时间：
1999
期刊：
Investigative ophthalmology & visual science.
影响因子：
--
作者：
Merbs,SL;Sidransky,D
通讯作者：
Sidransky,D