Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.
Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.
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DOI：
10.1093/nar/gkab053
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发表时间：
2021-03-18
影响因子：
14.9
通讯作者：
Jariel-Encontre I
中科院分区：
文献类型：
--
作者：
Bejjani F;Tolza C;Boulanger M;Downes D;Romero R;Maqbool MA;Zine El Aabidine A;Andrau JC;Lebre S;Brehelin L;Parrinello H;Rohmer M;Kaoma T;Vallar L;Hughes JR;Zibara K;Lecellier CH;Piechaczyk M;Jariel-Encontre I
无处不在的二聚体转录因子AP-1家族由FOS和JUN系列蛋白组成。长期以来，人们一直认为它主要是在基因启动子中运作，并且它如何控制转录仍然不理解。 FOS家族蛋白FRA-1在三重阴性乳腺癌（TNBC）中过表达，在那里它有助于肿瘤侵袭性。为了解决其在TNBC中的转录作用，我们结合了转录组学，芯片序列，机器学习和NG Capture-C。此外，我们研究了其FOS家族Kin Fra-2在TNBC中也表示，尽管少得多。与它们的多效效应一致，FRA-1和FRA-2向上和下调单独和下调，或冗余地与许多与广泛的生物学过程相关的基因。靶基因调节主要是由于在远离同源启动子的调节元素上结合了FRA-1和FRA-2，在该调节元件上，FRA-1调节转录共调节器p300/cbp的募集以及AP-1变体识别的差异可以是优先的FRA-1-或FRA-2结合。我们的工作在靶基因基因座的染色质体系结构控制中也没有表现出FRA-1的主要作用，但建议在染色质集线器中遇到FRA-1结合的增强子之间的合作，有时包括其他FRA-1调节基因的启动子。我们的工作影响了我们对AP-1的看法。
The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1.
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影响因子：
3.8
作者：
Chiappetta, Gennaro;Ferraro, Angelo;Botti, Gerardo;Monaco, Mario;Pasquinelli, Rosa;Vuttariello, Emilia;Arnaldi, Liliane;Di Bonito, Maurizio;D'Aiuto, Giuseppe;Pierantoni, Giovanna Maria;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
30.8
作者：
Allahyar, Amin;Vermeulen, Carlo;de Laat, Wouter
通讯作者：
de Laat, Wouter
影响因子：
8
作者：
Belguise, K;Kersual, N;Chalbos, D
通讯作者：
Chalbos, D
影响因子：
8
作者：
Belguise, K.;Milord, S.;Chalbos, D.
通讯作者：
Chalbos, D.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y