FAM122A Inhibits Erythroid Differentiation through GATA1

FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while...

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Bibliographic Details
Published in:Stem cell reports 2020-09, Vol.15 (3), p.721-734
Main Authors: Chen, Jing, Zhou, Qiong, Liu, Man-Hua, Yang, Yun-Sheng, Wang, Yin-Qi, Huang, Ying, Chen, Guo-Qiang
Format: Article
Language:English
Subjects:
erythroid differentiation
FAM122A
GATA1
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Summary:FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression significantly inhibits erythrocytic differentiation in primary human hematopoietic progenitor cells and erythroleukemia cells. Mechanistically, FAM122A directly interacts with the C-terminal zinc finger domain of GATA1, a critical transcriptional factor for erythropoiesis, and reduces GATA1 chromatin occupancy on the promoters of its target genes, thus resulting in the decrease of GATA1 transcriptional activity. The public datasets show that FAM122A is abnormally upregulated in patients with β-thalassemia. Collectively, our results demonstrate that FAM122A plays an inhibitory role in the regulation of erythroid differentiation, and it would be a potentially therapeutic target for GATA1-related dyserythropoiesis or an important regulator for amplifying erythroid cells ex vivo. •FAM122A inhibits terminal erythroid differentiation•FAM122A directly interacts with GATA1•FAM122A suppresses the DNA binding and transcriptional activities of GATA1•FAM122A is downregulated during terminal erythroid differentiation In this article, G.-Q. Chen and his colleagues show that FAM122A, a highly conserved housekeeping gene, inhibits terminal erythroid differentiation through suppressing the DNA binding and transcriptional activities of GATA1. This study proposes that FAM122A may be a potentially therapeutic target for GATA1-related dyserythropoietic disorders or an important regulator for amplifying erythroid cells ex vivo.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2020.07.010