Varghese P, Garcia-Cuellar MP, Slany R (2025)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2025
Book Volume: 151
Article Number: 104864
DOI: 10.1016/j.exphem.2025.104864
Open Access Link: https://www.exphem.org/article/S0301-472X(25)00155-9/fulltext
Transcription factor networks are critical hubs for organ development. Here, we investigated the hematopoietic function of the E-twenty six (Ets)-family transcription factor E74-like factor 1 (Elf1) that is normally predominantly expressed in monocytes. Strikingly, Elf1 was not only a direct downstream target of homeobox A9 (HoxA9) and leukemogenic mixed-lineage leukemia (MLL) fusion proteins but it was also consistently overexpressed in acute myeloid leukemia (AML) regardless of the underlying genotypic alteration. Chromatin immunoprecipitation localized Elf1 to archetypical myeloid enhancers and promoters as defined by colocalization with HoxA9 and Meis1. In perturbation/ectopic expression experiments Elf1 controlled a characteristic transcriptional program dominated by genes with a function in innate immunity. Importantly, in functional assays Elf1 was crucial for the rapid transcriptional response of myeloid cells toward lipopolysaccharide as demonstrated by upregulation of NfkB and RelB. This activity could be assigned to genomic control elements that bound Elf1 in vitro and in vivo and it was confirmed in myelocytes with a genetic knockout of Elf1. These results give insight into the architecture of the common hematopoietic enhancer where redundant binding of transcription factors may be explained by special requirements that appear only under certain conditions.
APA:
Varghese, P., Garcia-Cuellar, M.-P., & Slany, R. (2025). The myeloid transcription factor Elf1 regulates genes with function in innate immunity. Experimental Hematology, 151. https://doi.org/10.1016/j.exphem.2025.104864
MLA:
Varghese, Prabha, Maria-Paz Garcia-Cuellar, and Robert Slany. "The myeloid transcription factor Elf1 regulates genes with function in innate immunity." Experimental Hematology 151 (2025).
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