FAM122A Inhibits Erythroid Differentiation through GATA1
| Autor: | Qiong Zhou, Jing Chen, Guo-Qiang Chen, Yin-Qi Wang, Ying Huang, Man-Hua Liu, Yun-Sheng Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcription Genetic Regulator Down-Regulation Antigens CD34 Biology Biochemistry Article 03 medical and health sciences 0302 clinical medicine Erythroid Cells Downregulation and upregulation GATA1 hemic and lymphatic diseases Genetics Humans Erythropoietin Zinc finger erythroid differentiation Intracellular Signaling Peptides and Proteins Cell Differentiation Zinc Fingers Promoter DNA Cell Biology Phosphoproteins Chromatin Cell biology Housekeeping gene 030104 developmental biology Erythropoiesis K562 Cells FAM122A 030217 neurology & neurosurgery Protein Binding Developmental Biology |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | 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. Highlights • 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|