WDR5, ASH2L, and RBBP5 control the efficiency of FOS transcript processing.
WDR5, ASH2L, and RBBP5 control the efficiency of FOS transcript processing.
复制标题
DOI：
10.2478/s11658-014-0190-8
复制
发表时间：
2014-06
影响因子：
8.3
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Teoh PL;Sharrocks AD
H3K4 三甲基化与活性转录密切相关。该标记的沉积由 SET 域甲基转移酶催化，该酶由包含 WDR5、ASH2L 和 RBBP5 的子复合体（WAR 子复合体）组成；催化SET结构域蛋白；和额外的复杂特异性亚基。 ERK MAPK 通路还通过转录因子、共调节因子或组蛋白修饰复合物的磷酸化在基因调控中发挥重要作用。然而，这两种途径之间的潜在相互作用在很大程度上仍未被探索。我们研究了它们在即早基因（IEG）调控网络调控方面的潜在相互作用。我们发现 WAR 子复合体成分的耗尽导致 IEG 未剪接转录本水平增加，但这并不一定反映其成熟转录本的变化。这种情况的发生方式与启动子区域 H3K4me3 水平的变化无关。我们关注 FOS，发现 WAR 子复合体组件的耗尽影响了 FOS 转录处理的效率。我们的研究结果显示了 WAR 子复合体在协调活性转录与有效的前 mRNA 加工方面的新功能。本文的补充材料可在 10.2478/s11658-014-0190-8 上获取，授权用户可以访问。
H3K4 trimethylation is strongly associated with active transcription. The deposition of this mark is catalyzed by SET-domain methyltransferases, which consist of a subcomplex containing WDR5, ASH2L, and RBBP5 (the WAR subcomplex); a catalytic SET-domain protein; and additional complexspecific subunits. The ERK MAPK pathway also plays an important role in gene regulation via phosphorylation of transcription factors, co-regulators, or histone modifier complexes. However, the potential interactions between these two pathways remain largely unexplored. We investigated their potential interplay in terms of the regulation of the immediate early gene (IEG) regulatory network. We found that depletion of components of the WAR subcomplex led to increased levels of unspliced transcripts of IEGs that did not necessarily reflect changes in their mature transcripts. This occurs in a manner independent from changes in the H3K4me3 levels at the promoter region. We focused on FOS and found that the depletion of WAR subcomplex components affected the efficiency of FOS transcript processing. Our findings show a new aspect of WAR subcomplex function in coordinating active transcription with efficient pre-mRNA processing. Supplementary material is available for this article at 10.2478/s11658-014-0190-8 and is accessible for authorized users.
登录
查看更多内容
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
4.8
作者：
Lee, JH;Skalnik, DG
通讯作者：
Skalnik, DG
影响因子：
9.8
作者：
Hazzalin, CA;Mahadevan, LC
通讯作者：
Mahadevan, LC
影响因子：
16
作者：
Hughes, CM;Rozenblatt-Rosen, O;Meyerson, M
通讯作者：
Meyerson, M
影响因子：
5.4
作者：
Mishra, Bibhu P.;Ansari, Khairul I.;Mandal, Subhrangsu S.
通讯作者：
Mandal, Subhrangsu S.