Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans.
Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans.
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DOI：
10.1093/nar/gki705
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发表时间：
2005
影响因子：
14.9
通讯作者：
Lalande M
中科院分区：
文献类型：
--
作者：
Landers M;Calciano MA;Colosi D;Glatt-Deeley H;Wagstaff J;Lalande M
Angelman综合征（AS）是一种神经遗传性疾病，其特征是严重的智力低下、“木偶样”共济失调步态伴手臂运动不稳、癫痫发作、脑电图异常、多动和阵发性不适当的笑声。AS患者不能遗传编码泛素蛋白连接酶E3 A（UBE 3A）基因的正常活性母体拷贝。UBE 3A主要由脑中的母体等位基因转录，但在大多数其他组织中由两种等位基因表达。已经提出父本UBE 3A等位基因的脑特异性沉默由大的（>500 kb）父本非编码反义转录物（UBE 3A-ATS）介导。还有其他几个涉及反义转录物的印记调节的例子，它们具有两个主要特性：（i）反义转录物抑制正义转录物，（ii）正义和反义之间的相互作用顺式发生。我们在这里表明，在AS的小鼠模型中，Ube 3a突变的母系传递导致父系Ube 3a-ATS的表达增加，这表明反义是由正义而不是相互调节模式调节的。我们的观察，Ube 3a调节Ube 3a-ATS的表达在反式是在相反的正义反义表观遗传顺式相互作用的其他情况下，反对Ube 3a-ATS在Ube 3a的印记的主要作用。
Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, ‘puppet-like’ ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). UBE3A is transcribed predominantly from the maternal allele in brain, but is expressed from both alleles in most other tissues. It has been proposed that brain-specific silencing of the paternal UBE3A allele is mediated by a large (>500 kb) paternal non-coding antisense transcript (UBE3A-ATS). There are several other examples of imprinting regulation involving antisense transcripts that share two main properties: (i) the sense transcript is repressed by antisense and (ii) the interaction between sense and antisense occurs in cis. We show here that, in a mouse model of AS, maternal transmission of Ube3a mutation leads to increased expression of the paternal Ube3a-ATS, suggesting that the antisense is modulated by sense rather than the reciprocal mode of regulation. Our observation that Ube3a regulates expression of Ube3a-ATS in trans is in contrast to the other cases of sense–antisense epigenetic cis-interactions and argues against a major role for Ube3a-ATS in the imprinting of Ube3a.
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影响因子：
46.9
作者：
Rosok, O;Sioud, M
通讯作者：
Sioud, M
影响因子：
14.9
作者：
Landers, M;Bancescu, DL;Lalande, M
通讯作者：
Lalande, M
DOI：
10.1073/pnas.96.16.9258
发表时间：
1999-08-03
影响因子：
11.1
作者：
Gabriel, JM;Merchant, M;Nicholls, RD
通讯作者：
Nicholls, RD
影响因子：
3.5
作者：
Kashiwagi, A;Meguro, M;Oshimura, M
通讯作者：
Oshimura, M
影响因子：
4.8
作者：
Hatada, I;Nabetani, A;Mukai, T
通讯作者：
Mukai, T