RETRACTED: MZF1 regulates α-globin gene transcription via long-range interactions in erythroid differentiation (Retracted Article)

作者：Li, Haoli; Zeng, Jingjing; Zhao, Yongzhong; Xu, Xiangmin^*

来源：Blood Cells, Molecules, and Diseases, 2021, 87: 102533.

DOI：10.1016/j.bcmd.2020.102533

• Multi-omics integration
• alpha-Globin gene regulation
• Long-range interactions
• Chromatin immunoprecipitation assay
• Chromosome conformation capture assay
• Erythroid differentiation

Precise spatiotemporal gene expression regulation is crucial for human erythropoiesis. However, dramatic changes in the chromatin structure and transcriptome involved in alpha-globin gene expression during erythropoiesis still not fully understand. To identify candidate regulators for alpha-globin gene regulation, we carried out an integrated approach by integrating publicly available transcriptomic and epigenomic data. We computed active enhancers by overlapping enriched regions marked with H3K4me1 and H3K27ac and correlated their activity with mRNA expression. Next, we cataloged potential transcription factors via de novo motif analysis. We highlighted the discovery of potential novel transcription factor MZF1 of the alpha-globin gene in erythroid differentiation. To validate the role of MZF1, we quantified the expression level of MZF1 and alpha-globin gene in HSPCs, early erythroid progenitors and late erythroid precursors cells. Both the mRNA and protein expression patterns of MZF1 were consistent with the alpha-globin gene. Also, the qPCR result showed that the expression of the alpha-globin gene was significantly increased by the MZF1 overexpression. To further investigate the role of MZF1 regulating alpha-globin gene transcriptional activity during erythroid differentiation, we performed ChIP-qPCR at the alpha-globin locus. Our results showed that MZF1 recruitment both at 4 upstream HS sites and alpha-globin gene promoter in erythroid precursor cells. To determine the importance of the MZF1 to enhancer-promoter interaction at the alpha-globin locus, we compared interaction frequency before and after knockdown of MZF1 by chromosome conformation capture (3C) assay. Upon MZF1 depletion, both the expression of the alpha-globin gene and all 3C signals were significantly decreased. Taken together, MZF1 plays an important role in regulating alpha-globin gene expression by binding to long-region enhancers and alpha-globin gene promoter and facilitates the organization of specific 3D chromatin architecture in erythroid differentiation.

• 单位
  深圳市第二人民医院; 南方医科大学