Shared Transcriptional Machinery at Homologous Alleles Leads to Reduced Transcription in Early Drosophila Embryos.
Shared Transcriptional Machinery at Homologous Alleles Leads to Reduced Transcription in Early Drosophila Embryos.
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DOI：
10.3389/fcell.2022.912838
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
转录机制被招募到增强子和启动子来调节基因表达的机制是现代生物学中最具挑战性和最广泛研究的问题之一。我们探索了两个同源等位基因之间的等位基因间相互作用可能影响基因调控的可能性。使用基于MS2和PP7的、等位基因特异性的实时成像分析，我们在半合子和纯合子果蝇胚胎中可视化了报告基因的从头转录。令人惊讶的是，每个纯合子等位基因比相应的半合子等位基因产生的RNA更少，这表明纯合子中存在等位基因竞争的可能性。然而，当通过将报告构建置于不同的染色体位置或通过将增强子进一步远离启动子而削弱增强子-启动子相互作用时，没有观察到竞争。此外，当部分转录单位(增强子或报告基因)处于同源位置时，报告基因的转录活性降低。我们认为，结合增强子和启动子区域的转录机制，如RNA POL II或预起始复合体，可能是等位基因竞争的原因。我们发现，随着发育时间的延长，等位基因干扰的程度会增加，因为激活合子基因需要更多的POL II。对一种内源基因也观察到了这种等位基因竞争。我们的研究为3D等位基因间相互作用在基因调控中的作用提供了新的见解。
The mechanism by which transcriptional machinery is recruited to enhancers and promoters to regulate gene expression is one of the most challenging and extensively studied questions in modern biology. We explored the possibility that interallelic interactions between two homologous alleles might affect gene regulation. Using an MS2- and PP7-based, allele-specific live imaging assay, we visualized de novo transcripts of a reporter gene in hemizygous and homozygous Drosophila embryos. Surprisingly, each homozygous allele produced fewer RNAs than the corresponding hemizygous allele, suggesting the possibility of allelic competition in homozygotes. However, the competition was not observed when the enhancer-promoter interaction was weakened by placing the reporter construct in a different chromosome location or by moving the enhancer further away from the promoter. Moreover, the reporter gene showed reduced transcriptional activity when a partial transcription unit (either an enhancer or reporter gene only) was in the homologous position. We propose that the transcriptional machinery that binds both the enhancer and promoter regions, such as RNA Pol II or preinitiation complexes, may be responsible for the allelic competition. We showed that the degree of allelic interference increased over developmental time as more Pol II was needed to activate zygotic genes. Such allelic competition was observed for an endogenous gene as well. Our study provides new insights into the role of 3D interallelic interactions in gene regulation.
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影响因子：
14.9
作者：
Larkin A;Marygold SJ;Antonazzo G;Attrill H;Dos Santos G;Garapati PV;Goodman JL;Gramates LS;Millburn G;Strelets VB;Tabone CJ;Thurmond J;FlyBase Consortium
通讯作者：
FlyBase Consortium
DOI：
10.1126/science.1202142
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Larson DR;Zenklusen D;Wu B;Chao JA;Singer RH
通讯作者：
Singer RH
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
7.7
作者：
Cho, Won-Ki;Jayanth, Namrata;Cisse, Ibrahim I.
通讯作者：
Cisse, Ibrahim I.
影响因子：
7.7
作者：
Berrocal A;Lammers NC;Garcia HG;Eisen MB
通讯作者：
Eisen MB