GSE156198 Histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development

Contributors : Apratim Mitra ; Danny Stamos ; Lauren Clubb ; Jan Lee ; Dalal El-Khoury ; Paul E LoveSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusEarly T cell development involves the stepwise maturation of thymus seeding progenitors that resemble multipotent hematopoietic stem/progenitor cells (HSPCs) into T-lineage committed cells. Analysis of the transcriptional profiles of developing thymocytes has shown that T-lineage commitment is associated with loss of early HSPC gene signatures and acquisition of T cell gene signatures. Less well understood are the epigenetic alterations that accompany or enable these transcriptional changes. Here, we show that the histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing the HSPC transcriptional program during thymocyte maturation. Massive up-regulation of progenitor genes in Lsd1 deficient thymocytes was associated with increased H3K4 tri-methylation at gene promoters. Deletion of Lsd1 caused a block in late T cell development and over-expression of Gfi1 and Blimp1 repressor targets including the checkpoint molecules PD-1, Ctla4 and Nrp1. These results reveal a critical function for Lsd1-mediated H3K4 demethylation in regulating gene expression during T cell development.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research