| First Author | Kasper LH | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 7 | Pages | e102076 |
| PubMed ID | 25054639 | Mgi Jnum | J:217860 |
| Mgi Id | MGI:5615958 | Doi | 10.1371/journal.pone.0102076 |
| Citation | Kasper LH, et al. (2014) T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs. PLoS One 9(7):e102076 |
| abstractText | MED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-responsive genes, the constituents of which vary between cell types for reasons that are not completely clear. MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown. We generated Med23 conditional knockout mice and induced Med23 deletion in early T-cell development using the lineage specific Lck-Cre transgene. While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T-cell master regulatory transcription factor. Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects. Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression. In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2. |
