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位于11p15印记区域中心的两个新基因逃避了基因组印记。

Two novel genes in the center of the 11p15 imprinted domain escape genomic imprinting.

作者信息

Lee M P, Brandenburg S, Landes G M, Adams M, Miller G, Feinberg A P

机构信息

Department of Medicine, Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205, USA.

出版信息

Hum Mol Genet. 1999 Apr;8(4):683-90. doi: 10.1093/hmg/8.4.683.

DOI:10.1093/hmg/8.4.683
PMID:10072438
Abstract

We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from human chromosome 11p15 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of two novel cDNAs, designated here as TSSC4 and TSSC6 (tumor-suppressing STF cDNA 4 and 6), located within the STF. TSSC4 and TSSC6 encode predicted proteins of 329 and 290 amino acids, respectively, with no close similarity to previously reported proteins. TSSC4 and TSSC6 are both located in the center of a 1 Mb imprinted domain, which contains the imprinted genes TSSC3, TSSC5, p57(KIP2), KVLQT1, ASCL2, IGF2 and H19. However, we found that neither TSSC4 nor TSSC6 was significantly imprinted in any of the fetal or extra-embryonic tissues examined. Based on this result, the imprinted gene domain of 11p15 appears to contain at least two imprinted subdomains, between which TSSC4 and TSSC6 substantially escape imprinting, due either to lack of initial silencing or to an early developmental relaxation of imprinting.

摘要

我们先前报道了从人类11号染色体p15区域分离出一个2.5 Mb的肿瘤抑制亚染色体可转移片段(STF),并鉴定出该STF内的9个已知基因和4个新基因。我们现在报道在该STF内分离出两个新的cDNA,分别命名为TSSC4和TSSC6(肿瘤抑制STF cDNA 4和6)。TSSC4和TSSC6分别编码预测的含有329和290个氨基酸的蛋白质,与先前报道的蛋白质没有密切的相似性。TSSC4和TSSC6均位于一个1 Mb印记结构域的中心,该结构域包含印记基因TSSC3、TSSC5、p57(KIP2)、KVLQT1、ASCL2、IGF2和H19。然而,我们发现在所检测的任何胎儿或胚外组织中,TSSC4和TSSC6均未发生明显的印记。基于这一结果,11p15的印记基因结构域似乎包含至少两个印记亚结构域,TSSC4和TSSC6在这两个亚结构域之间基本上逃避了印记,这可能是由于缺乏初始沉默或印记在早期发育过程中松弛所致。

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