EloA promotes HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity

Abstract

Megakaryocytes (MKs) are the unique non-pathological cells that undergo polyploidization in mammals. The polyploid formation is critical for understanding the MK biology, and transcriptional regulation is involved in the differentiation and maturation of MKs. However, little is known about the functions of transcriptional elongation factors in the MK polyploidization. In this study, we investigated the role of transcription elongation factor EloA in the polyploidy formation during the MK differentiation. We found that EloA was highly expressed in the erythroleukemia cell lines HEL and K562. Knockdown of EloA in HEL cell line was shown to impair the phorbol myristate acetate (PMA) induced polyploidization process, which was used extensively to model megakaryocytic differentiation. Selective over-expression of EloA mutants with Pol II elongation activity partially restored the polyploidization. RNA-sequencing revealed that knockdown of EloA decelerated the transcription of genes enriched in the ERK1/2 cascade pathway. The phosphorylation activity of ERK1/2 decreased upon the EloA inhibition, and the polyploidization process of HEL was hindered when ERK1/2 phosphorylation was inhibited by PD0325901 or SCH772984. This study evidenced a positive role of EloA in HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity.

Keywords:

• EloA
• ERK1/2
• megakaryocytic difffferentiation
• polyploidization
• transcription elongation factor

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81770197 and 81903838), Young talents program of Chongqing (T03010008), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0051) and Clinical Research Funding of the Second Affiliated Hospital of the Army Medical University (2016YLC04).

Disclosure statement

The authors declare no competing financial interests.

Author contributions

L. Chen. and Z. J. Li. designed the research; L. Chen., L. Y. Hu., W. W. Zhang., Z. Xiang., Y. L. Wang., C. Zeng., X. J. Wang., C. N. Tan., and Y. C. Zhang. performed the research; L. Chen., L. Y. Hu., W. W. Zhang., and Z. J. Li. analyzed the data; F. J. Li., Y. N. Xiao., L. P. Zhou., J. X. Li., C. Wu., Y. Xiang., L. X. Xiang., X. M. Zhang., X. Y. Wang., W. C. Yang., and Q. Ran. assisted with the experiments; L.Chen., L. Y. Hu., and M. S. Chen. wrote the paper.

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Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

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Funding

The author(s) reported that there is no funding associated with the work featured in this article.