All-trans Retinoic Acid Regulates Erythroid Differentiation of K562 Cells via Epigenetic Mechanisms
10.13865/j.cnki.cjbmb.2024.09.1156
- VernacularTitle:全反式维甲酸调控K562细胞红系分化的表观遗传机制
- Author:
Chun-Ya LIU
1
;
Bing-Hao JIA
;
Qin TANG
;
Yuan-Tian SUN
;
Li-Cheng REN
Author Information
1. 海南医科大学,基础医学与生命科学学院,热带转化医学教育部重点实验室,生物学教研室,海口 571199
- Keywords:
all-trans retinoic acid(ATRA);
erythroid differentiation;
chromatin conformational cap-ture;
chromatin immunoprecipitation(ChIP);
regulation of gene expression
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(10):1441-1452
- CountryChina
- Language:Chinese
-
Abstract:
All-trans retinoic acid(ATRA)is able to induce promyelocytic differentiation effectively.However,its role in the process of erythroid differentiation remains unclear.To investigate the role of AT-RA in the process of erythroid differentiation and its epigenetic regulatory mechanism,we established an induced leukemia cell K562 model in this study.Firstly,hemin was used to induce the differentiation of K562 cells into erythroid cells.The results of flow cytometry showed that ATRA affected the lineage changes of cells during erythroid differentiation and blocked the process of cell differentiation.After AT-RA treatment of differentiating cells,the expression level of erythroid differentiation-related genes de-creased.Through chromatin conformational capture(3C),formaldehyde-assisted separation of regulatory elements(FAIRE),chromatin immunoprecipitation(ChIP)techniques,the epigenetic mechanism was explored and it was found that after ATRA treatment of cells,the chromatin accessibility within the β-glo-bin family gene locus decreased,and the frequency of interaction between the locus control region(LCR)and its target gene promoter decreased.The decrease in the chromatin accessibility of the gene locus led to a decrease in the enrichment frequency of erythroid-related transcription factors GATA binding protein 1(GATA1),LIM domain binding 1(LDB1),LIM domain only 2(LMO2),and BHLH transcription factor 1(TAL1)at the promoter regions of the LCR and the gene locus of the globin family.The above results indicate that the ATRA treatment of differentiating cells leads to a decrease in the chromatin acces-sibility of erythroid differentiation-related genes,and a more closed chromatin structure hinders the bind-ing of LCR-recruiting transcription factors to the promoter regions of genes,thereby further repressing the expression of β-globin family genes.This dynamic process elucidates the epigenetic mechanism of ATRA in regulating erythroid differentiation.
