Histone Demethylase LSD1-Mediated Repression of GATA-2 Is Critical for Erythroid Differentiation

GATA-2 transcription factor is predominantly expressed in hematopoietic stem and progenitor cells (HS/PCs), and counteracts erythroid specific transcription factor GATA-1 to modulate proliferation and differentiation of hematopoietic cells. During hematopoietic cell differentiation, GATA-2 exhibits dynamic expression patterns, regulated by collaborations between GATA-1 and epigenetic regulators. Here, we show that histone specific demethylase1 (LSD1) regulates the expression of GATA-2 gene during erythroid differentiation. Knockdown of LSD1 leads to increased GATA-2 expression and inhibits induced MEL and embryonic stem cell differentiation. Furthermore, we demonstrate that LSD1 binds at the 1S promoter of GATA-2 gene locus, and suppresses GATA-2 expression through histone demethylation. Thus, our data reveals that LSD1 mediates erythroid cell differentiation by epigenetic modification of GATA-2 gene locus.