Gunaratne P H, Nakao M, Ledbetter D H, Sutcliffe J S, Chinault A C
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genes Dev. 1995 Apr 1;9(7):808-20. doi: 10.1101/gad.9.7.808.
To examine the relationship between replication timing and differential gene transcription in tissue-specific and imprinted settings we have studied the replication timing properties of the human Prader-Willi syndrome (PWS) region on human chromosome 15q11-13. Interphase fluorescence in situ hybridization with an overlapping series of cosmid clones was used to map a PWS replication timing domain to a 500- to 650-kb region that includes the SNRPN gene. This PWS domain replicates late in lymphocytes but predominantly early in neuroblasts, with replication asynchrony observed in both tissues, and appears to colocalize with a genetically imprinted transcription domain showing prominent expression in the brain. A 5- to 30-kb deletion in the 5' region of SNRPN results in the loss of late replication control of this domain in lymphocytes when the deleted chromosome is inherited paternally. This potential allele-specific replication timing control region also appears to colocalize with a putative imprinting control region that has been shown previously to abolish the expression of three imprinted transcripts in this same region.
为了研究在组织特异性和印记背景下复制时间与基因转录差异之间的关系，我们研究了人类15号染色体q11 - 13上普拉德-威利综合征（PWS）区域的复制时间特性。使用一系列重叠的黏粒克隆进行间期荧光原位杂交，将一个PWS复制时间结构域定位到一个包含SNRPN基因的500至650 kb区域。这个PWS结构域在淋巴细胞中复制较晚，但在神经母细胞中主要较早复制，在两种组织中均观察到复制不同步，并且似乎与在大脑中显示出显著表达的基因印记转录结构域共定位。当缺失的染色体是父系遗传时，SNRPN 5'区域5至30 kb的缺失导致该结构域在淋巴细胞中失去后期复制控制。这个潜在的等位基因特异性复制时间控制区域似乎也与一个推定的印记控制区域共定位，该区域先前已被证明可消除同一区域中三个印记转录本的表达。
