| First Author | Adoue V | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 3 | Pages | 629-644.e8 |
| PubMed ID | 30737147 | Mgi Jnum | J:282406 |
| Mgi Id | MGI:6380822 | Doi | 10.1016/j.immuni.2019.01.003 |
| Citation | Adoue V, et al. (2019) The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses. Immunity 50(3):629-644.e8 |
| abstractText | Upon activation, naive CD4(+) T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1(-/-) naive CD4(+) T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1(-/-) Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes. Refined bioinformatic analyses suggest that these retrotransposons regulate Th1 gene cis-regulatory elements or act as Th1 gene enhancers. Thus, H3K9me3 deposition by SETDB1 ensures Th cell lineage integrity by repressing a repertoire of ERVs that have been exapted into cis-regulatory modules to shape and control the Th1 gene network. |
