DamID profiling of dynamic Polycomb-binding sites in Drosophila imaginal disc development and tumorigenesis.
DamID profiling of dynamic Polycomb-binding sites in Drosophila imaginal disc development and tumorigenesis.
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DOI：
10.1186/s13072-018-0196-y
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发表时间：
2018-06-05
影响因子：
3.9
通讯作者：
Classen AK
中科院分区：
文献类型：
--
作者：
La Fortezza M;Grigolon G;Cosolo A;Pindyurin A;Breimann L;Blum H;van Steensel B;Classen AK
在体内跟踪动态蛋白质-染色质相互作用是揭示发育和疾病中转录和表观遗传转变的关键。然而，体内源材料的有限可用性和异质组织组成给许多实验方法带来了挑战。在这里，我们将细胞类型特异性DamID-seq分析应用于果蝇图像盘，并使基于FLP/ fr的诱导可用于GAL驱动介导的特定细胞系靶向。在一个原理证明的方法中，我们利用普遍存在的DamID表达来描述在翅膀成像椎间盘发育和scrib肿瘤发生模型中polycomb结合位点的动态转变。我们发现Atf3和Ets21C是参与scrib肿瘤发生的新的Polycomb靶基因，并表明Atf3和AP-1转录因子调控靶基因以及绝缘子功能的调节在Polycomb靶位点的动态结合中起着至关重要的作用。我们通过对10只幼虫的翅膀影像盘样本进行DamID-seq分析，证实了这些发现。我们的研究为体内影像椎间盘小细胞群的强大分析开辟了道路，并为致瘤转化的转录反应背后的表观遗传变化提供了见解。本文的在线版本（10.1186/s13072-018-0196-y）包含补充材料，授权用户可以使用。
Tracking dynamic protein–chromatin interactions in vivo is key to unravel transcriptional and epigenetic transitions in development and disease. However, limited availability and heterogeneous tissue composition of in vivo source material impose challenges on many experimental approaches. Here we adapt cell-type-specific DamID-seq profiling for use in Drosophila imaginal discs and make FLP/FRT-based induction accessible to GAL driver-mediated targeting of specific cell lineages. In a proof-of-principle approach, we utilize ubiquitous DamID expression to describe dynamic transitions of Polycomb-binding sites during wing imaginal disc development and in a scrib tumorigenesis model. We identify Atf3 and Ets21C as novel Polycomb target genes involved in scrib tumorigenesis and suggest that target gene regulation by Atf3 and AP-1 transcription factors, as well as modulation of insulator function, plays crucial roles in dynamic Polycomb-binding at target sites. We establish these findings by DamID-seq analysis of wing imaginal disc samples derived from 10 larvae. Our study opens avenues for robust profiling of small cell population in imaginal discs in vivo and provides insights into epigenetic changes underlying transcriptional responses to tumorigenic transformation. The online version of this article (10.1186/s13072-018-0196-y) contains supplementary material, which is available to authorized users.
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影响因子：
7.7
作者：
Bunker BD;Nellimoottil TT;Boileau RM;Classen AK;Bilder D
通讯作者：
Bilder D
影响因子：
--
作者：
Blanco E;Ruiz-Romero M;Beltran S;Bosch M;Punset A;Serras F;Corominas M
通讯作者：
Corominas M
影响因子：
3.5
作者：
Cubeñas-Potts C;Corces VG
通讯作者：
Corces VG
影响因子：
7.3
作者：
Amoyel M;Anderson AM;Bach EA
通讯作者：
Bach EA
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J