Rapamycin-induced β-Globin Family Locus Remodeling Regulates the Gene Switching Expression
10.13865/j.cnki.cjbmb.2023.05.1658
- Author:
Lan XU
1
;
Yi-Shu XIAO
1
;
Chun-Ya LIU
1
;
Bing-Hao JIA
1
;
Le DU
1
;
Dong-Na LI
1
;
Li-Cheng REN
1
Author Information
1. Department of Biology, Hainan Medical University
- Publication Type:Journal Article
- Keywords:
chromatin accessibility;
chromatin interactions;
chromatin remodeling;
regulation of gene expression;
β-globin genes family
- From:
Chinese Journal of Biochemistry and Molecular Biology
2023;39(9):1322-1331
- CountryChina
- Language:Chinese
-
Abstract:
β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.
