KMT1E is a regulator of T cell development (P4542)

Abstract

Abstract The histone methyltransferase KMT1E has a demonstrated role in pluripotency, embryonic stem cell development, and melanoma formation, yet its role in T cell development has not been investigated. As T-cell development involves many stages of lineage commitment, we hypothesized that KMT1E may have a role in regulating these commitment stages. KMT1E is dynamically regulated during the stages of T-cell development, peaking at the DN2 through DN4 stages and dramatically waning as lineage commitment occurs. In order to further query the role of KMT1E in thymocyte development, we created conditional knockout animals in which KMT1E is deleted specifically in the T cell compartment (where the Cre recombinase is driven by the Lck promoter). Deletion of KMT1E caused a profound reduction in the numbers of DN1 (Lin-/CD44+/CD25-) cells in the thymus and single positive CD4 and CD8 cells in the thymus and spleen. In order to elucidate the genetic changes induced by KMT1E that may influence the observed phenotype, we performed microarray experiments on thymocyte precursors from the wild type and conditional knockout animals. Deletion of KMT1E had a modest effect on global gene expression, with only a small subset of the genes being upregulated. Currently we are examining the role of these genes mediating KMT1E’s function in early T cell development.