DNA methylation status of DNAJA4 is essential for human erythropoiesis

Abstract

Aims: To investigate DNA methylation patterns in early and terminal stages of erythropoiesis, and to explore the function of differentially methylated genes in erythropoiesis and erythroid disorders. Materials & methods: Differential analysis of DNA methylation and gene expression during erythropoiesis, as well as weighted gene coexpression network analysis of acute myeloid leukemia was performed. Results: We identified four candidate genes that possessed differential methylation in the promoter regions. DNAJA4 affected proliferation, apoptosis and enucleation during terminal erythropoiesis and was associated with the prognosis of acute myeloid leukemia. DNAJA4 was specifically highly expressed in erythroleukemia and is associated with DNA methylation. Conclusion:DNAJA4 plays a crucial role for erythropoiesis and is regulated via DNA methylation. Dysregulation of DNAJA4 expression is associated with erythroid disorders.

Tweetable abstract

DNAJA4 is a novel regulator of terminal erythropoiesis which is regulated by DNA methylation, and its dysregulated expression is closely associated with impaired erythropoiesis in erythroid disorders.

Keywords::

• acute myeloid leukemia
• DNAJA4
• DNA methylation
• gene expression
• human erythropoiesis
• weighted coexpression network analysis

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0341

X Wu and T Wang designed the overall project, analyzed the results and prepared the manuscript, with input from all co-authors. H Zhang performed the bioinformatic analysis and experiments with assistance from F Xue, H Zhao and L Chen. All authors contributed to and approved the final version of the manuscript.

Acknowledgments

The authors thank the participants of the study who made this work possible, the members of the Institute of System Biology of Erythrocyte Development at School of Life Sciences, Zhengzhou University and Department of Gastroenterology, Children’s Hospital affiliated to Zhengzhou University.

Financial & competing interests disclosure

This work was supported, in part, by grants from the Natural Science Foundation of China (82170116, 81870094 and 81900112), The Program for Science & Technology Innovation Talents in Universities of Henan Province (20HASTIT039), the Key Scientific and Technological Research Projects in Henan Province (222102310012) and 2021 science and technology development plan of Henan Province (212102310037). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was used in the creation of this manuscript.

Data sharing statement

The datasets analyzed during the current study are available in the GEO database (www.ncbi.nlm.nih.gov/gds/) and cBioPortal database (www.cbioportal.org/).