Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-01-10 Print Date: 2024-03-01 DOI:10.26508/lsa.202302282
Carmen Espejo-Serrano, Catriona Aitken, Beatrice F Tan, Danielle G May, Rachel J Chrisopulos, Kyle J Roux, Jeroen Aa Demmers, Samuel G Mackintosh, Joost Gribnau, Francisco Bustos, Cristina Gontan, Greg M Findlay
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引用次数: 0

Abstract

Protein ubiquitylation regulates key biological processes including transcription. This is exemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental gene expression by ubiquitylating the REX1 transcription factor and is mutated in an X-linked intellectual disability disorder. However, the precise mechanisms by which ubiquitylation drives specific transcriptional responses are not known. Here, we show that RNF12 is recruited to specific genomic locations via a consensus sequence motif, which enables co-localisation with REX1 substrate at gene promoters. Surprisingly, RNF12 chromatin recruitment is achieved via a non-catalytic basic region and comprises a previously unappreciated N-terminal autoinhibitory mechanism. Furthermore, RNF12 chromatin targeting is critical for REX1 ubiquitylation and downstream RNF12-dependent gene regulation. Our results demonstrate a key role for chromatin in regulation of the RNF12-REX1 axis and provide insight into mechanisms by which protein ubiquitylation enables programming of gene expression.

RNF12/RLIM E3 泛素连接酶的染色质靶向控制转录反应。
蛋白质泛素化调控着包括转录在内的关键生物过程。E3 泛素连接酶 RNF12/RLIM 就是一个例子,它通过泛素化 REX1 转录因子来控制发育基因的表达。然而,泛素化驱动特定转录反应的确切机制尚不清楚。在这里,我们发现 RNF12 通过一个共识序列基序被招募到特定的基因组位置,从而与 REX1 底物共同定位在基因启动子上。令人惊奇的是,RNF12 的染色质招募是通过一个非催化基本区实现的,其中包括一种以前未被认识到的 N 端自动抑制机制。此外,RNF12 染色质靶向对 REX1 泛素化和下游 RNF12 依赖性基因调控至关重要。我们的研究结果证明了染色质在 RNF12-REX1 轴调控中的关键作用,并深入揭示了蛋白质泛素化实现基因表达编程的机制。
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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