摘要
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 modifcations 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.
基金
This work was supported by the grants from National Key Research and Development Program of China(Grant number 2108YFA0107800)
National Natural Science Foundation of China(Grant numbers 81920108004,81770107,81702722,81470362 and 81700168)
National Postdoctoral Program for Innovative Talents(Grant number BX201700292)
Natural Science Foundation of Hunan Province(Grant num ber 2018JJ3703)
Science and Technology Key Project of Hunan Province(Grant number 2018SK21212)
Fundamental Research Funds for the Central Universities of Central South University(Grant number 2018zzts386).