FAM122A Inhibits Erythroid Differentiation through GATA1.

Abstract:

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Chen J,Zhou Q,Liu MH,Yang YS,Wang YQ,Huang Y,Chen GQ

doi

10.1016/j.stemcr.2020.07.010

subject

Has Abstract

pub_date

2020-09-08 00:00:00

pages

721-734

issue

3

issn

2213-6711

pii

S2213-6711(20)30287-3

journal_volume

15

pub_type

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