RCOR1, also known as REST Corepressor 1, is a transcription repressor that recruits and positions LSD1 and HDAC1/2 on chromatin to modify histone methylation and acetylation. It is involved in multiple biological processes such as transcription regulation, cell differentiation, and development. It also plays a role in various signaling pathways, and its dysregulation is associated with diseases [1,2,3,4,5,6,7,8]. Mouse models have been crucial in understanding its functions in vivo [5,7].

In murine studies, Rcor1 -deficient mice are profoundly anemic and die in late gestation. Definitive erythroid cells from these mutant mice arrest at the transition from proerythroblast to basophilic erythroblast, and the mutant proerythroblasts aberrantly express genes of the myeloid lineage as well as HSC-related genes. Blocking the CSF2-dependent phospho-Stat5 hypersensitivity pathway can partially reduce myeloid colony formation by Rcor1-deficient erythroid progenitors [5]. Conditional knockout of Rcor1 in adult mice leads to severe anemia due to a block in committed erythroid progenitor maturation, reduced B-cells with increased apoptosis (non-cell autonomous requirement for B-cell survival), absence of mature neutrophils, and an increase in monocytic cells. Rcor1-deficient monocytes show enhanced self-renewal and overexpress genes associated with HSC/progenitor cell expansion [7]. In a DLBCL cohort, novel deletions in RCOR1 are associated with unfavorable progression-free survival, and an RCOR1 loss-associated gene signature can identify a subgroup of patients with unfavorable overall survival [8].

In conclusion, RCOR1 is essential for normal myeloerythroid lineage differentiation, and its deficiency leads to hematopoietic disorders. In addition, its dysregulation is associated with DLBCL prognosis. Mouse models, especially KO and CKO models, have been instrumental in revealing these functions and disease associations, providing insights into the biological processes and potential therapeutic targets related to RCOR1.