show Abstracthide AbstractLoss of Setd1b in adult mice using both ubiquitous and hematopoietic-specific deletion strategies caused lethality arising from severe hematopoietic defects. To identify genes regulated by Setd1b in HSPCs we performed RNA-seq analysis of the LSK (Lin-, Sca+, Kit+) compartment in the bone marrow. Mice carrying heterozygous and homozygous conditional Setd1b alleles and Rosa26-Cre-ERT2 were treated with Tamoxifen for 6 days (4 days gavage - 3 days pause - 2 days gavage). Mice were sacrificed 3 days after the last treatment and RNA was isolated and processed for next generation sequencing. We found that Setd1b regulates key lineage specification components including Cebpa, Gata-1 and Klf-1. Overall design: HSPC (LSK) mRNA profiles of Setd1b control (heterozygous) and knockout (homozygous) littermates were generated 3 days after the last tamoxifen administration, in triplicates.