Transcript- and tissue-specific imprinting of a tumour suppressor gene.
Transcript- and tissue-specific imprinting of a tumour suppressor gene.
复制标题
肿瘤抑制基因的转录和组织特异性印记。
DOI：
10.1093/hmg/ddn322
复制
发表时间：
2009-01-01
影响因子：
3.5
通讯作者：
Oakey RJ
中科院分区：
文献类型：
--
作者：
Schulz R;McCole RB;Woodfine K;Wood AJ;Chahal M;Monk D;Moore GE;Oakey RJ
膀胱癌相关蛋白基因(BLCAP；以前的BC10)是一种肿瘤抑制因子，可以限制细胞增殖并刺激细胞凋亡。BLCAP蛋白或信使在多种人类癌症中下调或缺失。在小鼠和人中，BLCAP/BLCAP的第一个内含子含有不同的Neuronatin(NNAT/NNAT)基因。NNAT是一种印记基因，它唯一地表达于父系遗传的等位基因。之前的研究没有发现BlCap在老鼠或人类身上留下印记的证据。在这里，我们展示了BlCap在小鼠和人脑中的印记，但在其他小鼠组织中没有。此外，BlCap产生了多个不同的转录本，在小鼠和人类中都表现出相互的等位基因特异性表达。我们认为BLCAP的组织特异性印记是由于NNAT在脑中具有特别高的转录活性，就像先前对相似组织和印记的小鼠Commd1/U2af1-Rs1基因座所暗示的那样。对于Commd1/U2af1-Rs1，我们发现它也产生了不同的转录变体，具有相互的等位基因特异性表达。BLCAP的印记表达及其与NNAT在转录水平上的相互作用可能与人类的癌变有关。
The Bladder Cancer-Associated Protein gene (BLCAP; previously BC10) is a tumour suppressor that limits cell proliferation and stimulates apoptosis. BLCAP protein or message are downregulated or absent in a variety of human cancers. In mouse and human, the first intron of Blcap/BLCAP contains the distinct Neuronatin (Nnat/NNAT) gene. Nnat is an imprinted gene that is exclusively expressed from the paternally inherited allele. Previous studies found no evidence for imprinting of Blcap in mouse or human. Here we show that Blcap is imprinted in mouse and human brain, but not in other mouse tissues. Moreover, Blcap produces multiple distinct transcripts that exhibit reciprocal allele-specific expression in both mouse and human. We propose that the tissue-specific imprinting of Blcap is due to the particularly high transcriptional activity of Nnat in brain, as has been suggested previously for the similarly organized and imprinted murine Commd1/U2af1-rs1 locus. For Commd1/U2af1-rs1, we show that it too produces distinct transcript variants with reciprocal allele-specific expression. The imprinted expression of BLCAP and its interplay with NNAT at the transcriptional level may be relevant to human carcinogenesis.
登录
查看更多内容
影响因子：
3
作者：
Lau, Christopher;Ng, Lydia;Hawrylycz, Mike
通讯作者：
Hawrylycz, Mike
影响因子：
4.4
作者：
Evans, HK;Wylie, AA;Jirtle, RL
通讯作者：
Jirtle, RL
影响因子：
2.7
作者：
John, RM;Aparicio, SAJR;Surani, MA
通讯作者：
Surani, MA
影响因子：
56.9
作者：
Bourc'his, D;Xu, GL;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
30.8
作者：
Keshet, I;Schlesinger, Y;Simon, I
通讯作者：
Simon, I