Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.
Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.
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RNF12/RLIM E3泛素连接酶染色质靶向控制转录反应。
DOI：
10.26508/lsa.202302282
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发表时间：
2024-03
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
E3泛素连接酶RNF12/RLIM在智力障碍中发生突变，并控制发育基因的表达。我们发现RNF12的染色质靶向是底物泛素化和转录反应所必需的，这为泛素化调节基因表达的机制提供了洞察力。蛋白质泛素化调控包括转录在内的关键生物学过程。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，并在一种X连锁的智力障碍中发生突变。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，我们证明了RNF12是通过一个共同的序列基序被招募到特定的基因组位置的，这使得REx1底物能够在基因启动子上共同定位。令人惊讶的是，RNF12染色质募集是通过一个非催化碱性区域实现的，并且包含一个以前未被发现的N末端自抑制机制。此外，RNF12染色质靶向对于REx1泛素化和下游RNF12依赖的基因调控至关重要。我们的结果证明了染色质在RNF12-REx1轴调节中的关键作用，并提供了对蛋白质泛素化使基因表达编程的机制的洞察。
The E3 ubiquitin ligase RNF12/RLIM is mutated in intellectual disability and controls developmental gene expression. We show that chromatin targeting of RNF12 is required for substrate ubiquitylation and transcriptional responses, providing insight into mechanisms by which ubiquitylation regulates gene expression. 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.
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影响因子：
64.5
作者：
Jiao B;Ma H;Shokhirev MN;Drung A;Yang Q;Shin J;Lu S;Byron M;Kalantry S;Mercurio AM;Lawrence JB;Hoffmann A;Bach I
通讯作者：
Bach I
影响因子：
4.6
作者：
Bustos F;Espejo-Serrano C;Segarra-Fas A;Toth R;Eaton AJ;Kernohan KD;Wilson MJ;Riley LG;Findlay GM
通讯作者：
Findlay GM
影响因子：
14.9
作者：
Khan A;Fornes O;Stigliani A;Gheorghe M;Castro-Mondragon JA;van der Lee R;Bessy A;Chèneby J;Kulkarni SR;Tan G;Baranasic D;Arenillas DJ;Sandelin A;Vandepoele K;Lenhard B;Ballester B;Wasserman WW;Parcy F;Mathelier A
通讯作者：
Mathelier A
影响因子：
11.4
作者：
Ballabeni, A;Melixetian, M;Helin, K
通讯作者：
Helin, K
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS