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

Platelets 2022 Jul 04

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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.

Citation

Lanyue Hu, Weiwei Zhang, Zheng Xiang, Yali Wang, Cheng Zeng, Xiaojie Wang, Chengning Tan, Yichi Zhang, Fengjie Li, Yanni Xiao, Luping Zhou, Jiuxuan Li, Chun Wu, Yang Xiang, Lixin Xiang, Xiaomei Zhang, Xueying Wang, Wuchen Yang, Maoshan Chen, Qian Ran, Zhongjun Li, Li Chen. EloA promotes HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity. Platelets. 2022 Jul 04;33(5):755-763