ALLELE-SPECIFIC REPLICATION TIMING OF IMPRINTED GENE REGIONS
ALLELE-SPECIFIC REPLICATION TIMING OF IMPRINTED GENE REGIONS
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DOI：
10.1038/364459a0
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发表时间：
1993-07-29
期刊：
影响因子：
64.8
通讯作者：
CEDAR, H
中科院分区：
文献类型：
--
作者：
KITSBERG, D;SELIG, S;CEDAR, H
有几条证据表明，父系和母系的基因组在发育中的器官中可能有不同的表达模式1，这一点已被鉴定出的亲本印记在小鼠2-5中的内源基因所证实。人们对这一过程中涉及的确切机制知之甚少，但这两个等位基因之间的结构差异肯定会以某种方式提供顺式作用信号，指导双亲特定的转录。细胞周期复制时间是一个参数，已被证明与女性细胞中X染色体的组织特异性基因表达6、7和等位基因特异性转录模式8有关。为此，我们研究了包含印记基因Igf2、Igf2r、H19和Snrpn的小鼠染色体区域的复制时序模式。在所有这些位置，以及它们在人类基因组中的相应位置，两个同源等位基因异步复制，而且总是父亲的等位基因在早期复制。因此，印记基因似乎以不同的复制模式嵌入到大的DNA结构域中，这可能为父母的身份识别提供了结构印记。
SEVERAL lines of evidence suggest that the paternal and maternal genomes may have different expression patterns in the developing organism1 and this has been confirmed by the identification of endogenous genes that are parentally imprinted in the mouse2-5. little is known about the precise mechanisms involved in the process, but structural differences between the two alleles must somehow provide cis-acting signals for directing parental-specific transcription. Cell-cycle replication time is one parameter that has been shown to be associated with both tissue-specific gene expression6,7 and the allele-specific transcription patterns of the X chromosomes in female cells8. For this reason we have examined the replication timing patterns for the chromosomal regions containing the imprinted genes Igf2, Igf2r, Hl9 and Snrpn in the mouse. At all of these sites, and their corresponding positions in the human genome, the two homologous alleles replicate asynchronously and it is always the paternal allele that is early-replicating. Thus imprinted genes appear to be embedded in large DNA domains with differential replication patterns, which may provide a structural imprint for parental identity.