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Integration of transcription coregulator complexes with sequence-specific DNA-binding factor interactomes
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 4.7 ) Pub Date : 2021-08-21 , DOI: 10.1016/j.bbagrm.2021.194749
Niels Velthuijs 1 , Birgit Meldal 2 , Quinte Geessinck 1 , Pablo Porras 2 , Yulia Medvedeva 3 , Anatoliy Zubritskiy 3 , Sandra Orchard 4 , Colin Logie 1
Affiliation  

The domain of transcription regulation has been notoriously difficult to annotate in the Gene Ontology, partly because of the intricacies of gene regulation which involve molecular interactions with DNA as well as amongst protein complexes. The molecular function ‘transcription coregulator activity’ is a part of the biological process ‘regulation of transcription, DNA-templated’ that occurs in the cellular component ‘chromatin’. It can mechanistically link sequence-specific DNA-binding transcription factor (dbTF) regulatory DNA target sites to coactivator and corepressor target sites through the molecular function ‘cis-regulatory region sequence-specific DNA binding’. Many questions arise about transcription coregulators (coTF). Here, we asked how many unannotated, putative coregulators can be identified in protein complexes? Therefore, we mined the CORUM and hu.MAP protein complex databases with known and strongly presumed human transcription coregulators. In addition, we trawled the BioGRID and IntAct molecular interaction databases for interactors of the known 1457 human dbTFs annotated by the GREEKC and GO consortia. This yielded 1093 putative transcription factor coregulator complex subunits, of which 954 interact directly with a dbTF. This substantially expands the set of coTFs that could be annotated to ‘transcription coregulator activity’ and sets the stage for renewed annotation and wet-lab research efforts. To this end, we devised a prioritisation score based on existing GO annotations of already curated transcription coregulators as well as interactome representation. Since all the proteins that we mined are parts of protein complexes, we propose to concomitantly engage in annotation of the putative transcription coregulator-containing complexes in the Complex Portal database.



中文翻译:

转录共调节复合物与序列特异性 DNA 结合因子相互作用组的整合

众所周知,转录调控领域在基因本体论中很难注释,部分原因是基因调控的复杂性,涉及与 DNA 以及蛋白质复合物之间的分子相互作用。分子功能“转录共调节活性”是细胞成分“染色质”中发生的“DNA 模板转录调节”生物过程的一部分。它可以通过分子功能“顺式调节区序列特异性DNA结合”将序列特异性DNA结合转录因子(dbTF)调节DNA靶位点与共激活子和辅阻遏物靶位点机械地连接起来。关于转录共调节因子 (coTF) 存在许多问题。在这里,我们问在蛋白质复合物中可以鉴定出多少未注释的推定共调节因子?因此,我们利用已知的和强烈推测的人类转录共调节因子来挖掘 CORUM 和 hu.MAP 蛋白质复合物数据库。此外,我们还对 BioGRID 和 IntAct 分子相互作用数据库进行了搜索,寻找由 GREEKC 和 GO 联盟注释的已知 1457 个人类 dbTF 的相互作用子。这产生了 1093 个假定的转录因子辅助调节复合体亚基,其中 954 个直接与 dbTF 相互作用。这大大扩展了可注释为“转录共调节子活动”的 coTF 集,并为新的注释和湿实验室研究工作奠定了基础。为此,我们根据已策划的转录共调节子的现有 GO 注释以及相互作用组表示​​设计了优先级评分。由于我们挖掘的所有蛋白质都是蛋白质复合物的一部分,因此我们建议同时对 Complex Portal 数据库中假定的含有转录共调节因子的复合物进行注释。

更新日期:2021-08-24
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