Origins of extreme sexual dimorphism in genomic imprinting
Origins of extreme sexual dimorphism in genomic imprinting
复制标题
基因组印记中极端性别二态性的起源
DOI：
--
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发表时间：
2006
影响因子：
1.7
通讯作者：
T. Bestor
中科院分区：
文献类型：
--
作者：
Déborah Bourc'his;T. Bestor
大致相同数量的印记基因受到母本和父本等位基因的抑制。这掩盖了印记基因调控主要方面背后的强烈性别二态性。首先，印记在雄性生殖系中很早就建立，并持续到生物体的生殖寿命，而母本基因组印记在排卵前不久建立，并在下一代的原始生殖细胞中很快被消除。其次，许多 CpG 岛相关启动子会发生母源甲基化，但没有已知的启动子会发生父源特异性种系甲基化。少数已知的父系甲基化标记距离受影响的基因有数千个碱基，并且 CpG 密度较低。第三，在雌性生殖细胞中，Dnmt3L是印记建立所必需的，但不是转座子甲基化所必需的，而Dnmt3L是转座子甲基化所必需的，并且在雄性生殖细胞中印记位点的从头甲基化中仅起很小的作用。第四，母本表达的基因通常在父本等位基因上被顺式产生并编码非翻译RNA的父本表达的印记基因抑制。这里表明，高度可变的甲基化CpG位点的快速丢失导致了父系抑制的印记基因中甲基化靶位点的耗尽，并且基于RNA或调节位点正在进行的转录的局部抑制影响的印记机制已经进化以对抗父系甲基化调节区域的侵蚀。该突变模型基于以下事实：父系甲基化序列比母系甲基化序列保持甲基化状态的时间长得多，因此丢失的速度相应更快。印记建立时间的差异可能是印记基因表达其他方面日益增加的性别二态性的基础。
Roughly equal numbers of imprinted genes are subject to repression from alleles of maternal and of paternal origin. This masks the strong sexual dimorphism that underlies major aspects of imprinted gene regulation. First, imprints are established very early in the male germ line and persist for the reproductive life of the organism, while maternal genomic imprints are established shortly prior to ovulation and are erased soon thereafter in the primordial germ cells of the next generation. Second, many CpG island-associated promoters are subject to maternal methylation but no known promoters are subject to paternal-specific germline methylation. The few known paternal methylation marks are kilobases distant from the affected genes and have a low CpG density. Third, Dnmt3L is required for imprint establishment but not transposon methylation in female germ cells, while Dnmt3L is required for transposon methylation and has only a minor role in de novo methylation at imprinted loci in male germ cells. Fourth, maternally expressed genes are commonly repressed on the paternal allele by paternally expressed imprinted genes produced in cis and encoding nontranslated RNAs. It is here suggested that rapid loss of highly mutable methylated CpG sites has led to the depletion of methylation target sites in paternally repressed imprinted genes, and that an imprinting mechanism based on RNAs or local inhibitory influences of ongoing transcription of regulatory loci has evolved to counter the erosion of paternally methylated regulatory regions. This mutability model is based on the fact that paternally methylated sequences are maintained in the methylated state for a much longer time than are maternally methylated sequences, and are therefore lost at a correspondingly faster rate. The difference in timing of imprint establishment is likely to underlie the increasing sexual dimorphism of other aspects of imprinted gene expression.
DOI：
10.1073/pnas.81.17.5523
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
PACHNIS, V;BELAYEW, A;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
影响因子：
4.4
作者：
Davis, TL;Trasler, JM;Bartolomei, MS
通讯作者：
Bartolomei, MS