| First Author | Fang D | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 5 | Pages | 1449-1462 |
| PubMed ID | 29514917 | Mgi Jnum | J:261591 |
| Mgi Id | MGI:6155781 | Doi | 10.1084/jem.20171127 |
| Citation | Fang D, et al. (2018) Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation. J Exp Med 215(5):1449-1462 |
| abstractText | GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they colocalize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5, and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3 dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells. |
