| First Author | Yagi R | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 23 | Pages | 8087-97 |
| PubMed ID | 17908791 | Mgi Jnum | J:129048 |
| Mgi Id | MGI:3768583 | Doi | 10.1128/MCB.00631-07 |
| Citation | Yagi R, et al. (2007) Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils. Mol Cell Biol 27(23):8087-97 |
| abstractText | Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types. |
