| First Author | Stamos DB | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 12 | PubMed ID | 34726730 |
| Mgi Jnum | J:344063 | Mgi Id | MGI:7285847 |
| Doi | 10.1084/jem.20202012 | Citation | Stamos DB, et al. (2021) The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development. J Exp Med 218(12):e20202012 |
| abstractText | Analysis of the transcriptional profiles of developing thymocytes has shown that T lineage commitment is associated with loss of stem cell and early progenitor gene signatures and the 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 stem/progenitor transcriptional programs in addition to key repressive gene programs during thymocyte maturation. Deletion of Lsd1 caused a block in late T cell development and resulted in overexpression of interferon response genes as well as genes regulated by the Gfi1, Bcl6, and, most prominently, Bcl11b transcriptional repressors in CD4+CD8+ thymocytes. Transcriptional overexpression in Lsd1-deficient thymocytes was not always associated with increased H3K4 trimethylation at gene promoters, indicating that Lsd1 indirectly affects the expression of many genes. Together, these results identify a critical function for Lsd1 in the epigenetic regulation of multiple repressive gene signatures during T cell development. |
