SAMD1 directs the transcription of erythroid progenitors. (A) Heat map of CUT&RUN signal showing SAMD1 enrichment at SAMD1 peaks compared with IgG in HUDEP-2 cells (n = 11 798). (B) Annotation of SAMD1 peaks at genomic features in HUDEP-2 cells. (C) Annotation of SAMD1 peaks at significantly changing genes from the RNA-seq of sgSAMD1 vs sgControl erythroid progenitors. (D) Enriched motif at SAMD1-bound peaks. (E) Venn diagram of SAMD1 occupancy sites in HUDEP-2 and ES cells. (F) Table of co-occupied transcription factors with SAMD1 occupancy sites from publicly available chromatin immunoprecipitation (ChIP) data in HUDEP-2, K562, and primary erythroid progenitors. The signal for each peak is derived from 2 replicates. (G) CUT&RUN chromatin occupancy of SAMD1 at the L3MBTL3, GATA2, and BCL11A loci in HUDEP-2 cells. (H) Quantitative ChIP quantitative polymerase chain reaction (qPCR) at the L3MBTL3, GATA2, and BCL11A promoters in HUDEP-2 cells infected with scramble guides in IgG and SAMD1 ChIP ( = 4). (I) Normalized RNA-seq of sgControl and sgSAMD1 primary erythroid progenitors at day 12 of erythroid differentiation ( = 4). RNA-seq counts were normalized based on reads per kilobase per million mapped reads (transcripts per million [TPM]). (J) Western blot of GATA2 and actin in day-12 CD34⁺ progenitors. Error bars represent standard deviation (SD). ∗P < .05; ∗∗P < .01 (2-tailed unpaired Student t test). IgG, immunoglobulin G; UTR, untranslated region.