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多功能衔接蛋白Daxx与染色质重塑ATP酶Brg1相互作用。

Multifunctional adaptor protein Daxx interacts with chromatin-remodelling ATPase Brg1.

作者信息

Svadlenka Jan, Brazina Jan, Hanzlikova Hana, Cermak Lukas, Andera Ladislav

机构信息

Institute of Molecular Genetics AS CR, Czech Republic.

Department of Pathology, New York University School of Medicine, New York, USA.

出版信息

Biochem Biophys Rep. 2015 Dec 30;5:246-252. doi: 10.1016/j.bbrep.2015.12.012. eCollection 2016 Mar.

Abstract

Multifunctional adapter and chaperone protein Daxx participates in the regulation of a number of mainly transcription-related processes. Most notably in a complex with chromatin-remodelling ATPase ATRX, Daxx serves as a histone H3.3 chaperone at telomeric regions and certain genes. In this report we document that Daxx interacts with another chromatin-remodelling, ATPase Brg1. We confirm the Daxx-Brg1 association both in vitro and in cells and show that Daxx interacts with Brg1 in high-molecular-weight complexes. Ectopic co-expression of Daxx with Brg1 and PML could shift disperse nuclear localisation of Brg1 into PML bodies. Mapping the Daxx-Brg1 interaction revealed that Daxx preferentially binds the region between Brg1 N-terminal QLQ and HSA domains, but also weakly interacts with its C-terminal part. Brg1 interacted with both the central and N-terminal parts of Daxx. SiRNA-mediated down-regulation of Daxx in SW13 adrenal carcinoma cells markedly enhanced expression of Brg1-activated genes CD44 or SCEL, suggesting that Daxx either directly through Brg1 and/or indirectly via other factors is a negative regulator of their transcription. Our findings point to Brg1 as another chromatin-remodelling protein that might similarly, as ATRX, target Daxx to specific chromatin regions where it can carry out its chromatin- and transcription-regulating functions.

摘要

多功能衔接蛋白和伴侣蛋白Daxx参与多种主要与转录相关过程的调控。最显著的是,Daxx与染色质重塑ATP酶ATRX形成复合物,在端粒区域和某些基因处作为组蛋白H3.3伴侣蛋白发挥作用。在本报告中,我们记录了Daxx与另一种染色质重塑ATP酶Brg1相互作用。我们在体外和细胞内均证实了Daxx与Brg1的结合,并表明Daxx在高分子量复合物中与Brg1相互作用。Daxx与Brg1及PML的异位共表达可使Brg1的分散核定位转移至PML小体中。对Daxx与Brg1相互作用的定位分析显示,Daxx优先结合Brg1 N端QLQ和HSA结构域之间的区域,但也与其C端部分存在弱相互作用。Brg1与Daxx的中央部分和N端部分均相互作用。在SW13肾上腺癌细胞中,通过小干扰RNA介导下调Daxx可显著增强Brg1激活基因CD44或SCEL的表达,这表明Daxx可能直接通过Brg1和/或间接通过其他因子对其转录起负调控作用。我们的研究结果表明,Brg1作为另一种染色质重塑蛋白,可能与ATRX类似,将Daxx靶向特定的染色质区域,使其能够在其中发挥染色质和转录调控功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c8c/5600331/6a0a10344c6b/gr1.jpg

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