SAMD1 opposes and promotes LSD1 activity in erythroid progenitors. (A) Venn diagram of SAMD1 and LSD1 binding sites in scramble HUDEP-2 cells. (B) Change in H3K4me2 peak signal between sgControl and sgSAMD1 HUDEP-2 cells in the presence or absence of LSD1 (2-tailed unpaired Student t test). (C) Chromatin occupancy profile from CUT&RUN of SAMD1 and H3K4me2 at the GATA2, RUNX1, SPI1, and TAL1 loci in sgControl and sgSAMD1 HUDEP-2 cells (2-tailed paired Student t test). (D) Normalized RNA-seq of sgControl and sgSAMD1 primary erythroid progenitors at day 12 of erythroid differentiation (n = 4). RNA-seq counts were normalized based on reads per kilobase per million mapped reads (TPM). (E) mRNA levels of SLC4A1 and GATA2 after 24 hours of either dimethyl sulfoxide alone, 10 nM or 100 nM of GSK-LSD1 treatment in sgControl and sgSAMD1 HUDEP-2 cells (n = 6; 1-way analysis of variance). Not all statistically significant values in panel E are indicated. Error bars represent SD. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.