A pathogenic GATA2 zinc finger mutation restricts chromatin occupancy in human erythroid progenitor cells

The transcription factor GATA2 regulates hematopoietic stem and progenitor production and function via interactions with other regulatory proteins at gene enhancers and promoters. Genome-wide patterns of GATA2 chromatin occupancy differ by cell type; dynamically controlled by levels of GATA2 and associated proteins. During erythroid differentiation, gene expression networks that drive the process are established upon displacement of GATA2 from regulatory elements by the related transcription factor GATA1. Herein, we map sites of GATA2 chromatin occupancy in the human erythroid progenitor cell line HUDEP-2 and define the genes regulated by GATA2 in these cells. Additionally, we show that a human pathogenic GATA2 mutation, T354M, restricts GATA2 occupancy to a subset of chromatin sites. Overall design: Cut & Tag to detect GATA2 chromatin binding was performed on wild-type and GATA2-deficient HUDEP-2 cells following lentiviral expression of HA-tagged GATA2 or HA-tagged GATA2(T354M).