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Locus specific epigenetic modalities of random allelic expression imbalance
bioRxiv - Molecular Biology Pub Date : 2021-03-04 , DOI: 10.1101/2021.03.04.433808
Lucile Marion-Poll , Benjamin Forêt , Dina Zielinski , Florian Massip , Mikael Attia , Ava C Carter , Laurène Syx , Howard Y Chang , Anne-Valerie Gendrel , Edith Heard

Most autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression was not observed in ESCs, but when we assessed expression status in more than 200 clones of neuronal progenitor cells, we observed high frequencies of monoallelism. We uncovered unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up novel therapeutic perspectives.

中文翻译:

等位基因表达不平衡的基因座特定表观遗传方式

人们认为大多数常染色体基因均由两个等位基因表达,但有一些显着例外,包括印迹基因和显示随机单等位基因表达(RME)的基因。RME的范围和性质一直是争论的主题。在这里,我们研究了分化前后F1杂交小鼠细胞中几种候选RME基因的表达,以定义它们如何持续,单等位表达。在ESC中未观察到克隆单等位基因表达,但是当我们评估200多个神经元祖细胞克隆中的表达状态时,我们观察到了高频率的单等位基因。我们发现了基因表达和表观遗传调控的等位基因表达的不可预见的模式。这种非规范的等位基因调控对发育和疾病具有重要意义,
更新日期:2021-03-05
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