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Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Authors :
Zi Wang
Pan Wang
Yanan Li
Hongling Peng
Yu Zhu
Narla Mohandas
Jing Liu
Source :
Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-16 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
20593635
Volume :
6
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Signal Transduction and Targeted Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.65abb666e34417b71d6f2b495b0d9c
Document Type :
article
Full Text :
https://doi.org/10.1038/s41392-020-00422-1