FAM122A Inhibits Erythroid Differentiation through GATA1

Stem Cell Reports. 2020 Sep 8;15(3):721-734. doi: 10.1016/j.stemcr.2020.07.010. Epub 2020 Aug 6.

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.

Keywords: FAM122A; GATA1; erythroid differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • DNA / metabolism
  • Down-Regulation / genetics
  • Erythroid Cells / cytology*
  • Erythroid Cells / drug effects
  • Erythroid Cells / metabolism*
  • Erythropoietin / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • K562 Cells
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Binding / drug effects
  • Transcription, Genetic / drug effects
  • Zinc Fingers

Substances

  • Antigens, CD34
  • Intracellular Signaling Peptides and Proteins
  • PABIR1 protein, human
  • Phosphoproteins
  • Erythropoietin
  • DNA