Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies.
Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies.
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造血和血液恶性肿瘤中辅因子和转录因子之间的相互作用
DOI：
10.1038/s41392-020-00422-1
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发表时间：
2021-01-20
影响因子：
39.3
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Wang Z;Wang P;Li Y;Peng H;Zhu Y;Mohandas N;Liu J
造血需要在发育的每个阶段对基因表达进行微调调节。基因转录的调控不仅涉及单个转录因子，还涉及由转录因子和多亚基辅因子组成的转录复合物。在它们的正常组成中，TC协调谱系特异性的基因表达模式，并确保在造血过程中产生正确比例的单个细胞谱系。通过辅因子-TF相互作用，在染色质景观、核小体、组蛋白和相互作用组分中整合翻译后和构象修饰对最佳TF活性至关重要。辅因子基因的突变或易位预期会改变辅因子-TF相互作用，这可能是各种血液疾病发病机制的原因。通过靶向异常复合物中的辅因子来阻断血液系统疾病中的TF致癌活性一直是一种令人兴奋的治疗策略。在这篇综述中，我们总结了目前的知识有关的模型和功能的辅助因子TF相互作用的生理造血和突出其在血液系统恶性肿瘤的病因学的影响。本文综述了血液系统中转录机制的生理和病理意义。
Hematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.
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影响因子：
32.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
23.9
作者：
Aranda-Orgilles B;Saldaña-Meyer R;Wang E;Trompouki E;Fassl A;Lau S;Mullenders J;Rocha PP;Raviram R;Guillamot M;Sánchez-Díaz M;Wang K;Kayembe C;Zhang N;Amoasii L;Choudhuri A;Skok JA;Schober M;Reinberg D;Sicinski P;Schrewe H;Tsirigos A;Zon LI;Aifantis I
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