1. Id1 induces apoptosis through inhibition of RORgammat expression
- Author
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Xiao Hong Sun, Hong Cheng Wang, and Yuanzheng Yang
- Subjects
Inhibitor of Differentiation Protein 1 ,lcsh:Immunologic diseases. Allergy ,Receptors, Retinoic Acid ,Recombinant Fusion Proteins ,T-Lymphocytes ,T cell ,Cellular differentiation ,Transcription Factor 7-Like 1 Protein ,Immunology ,Apoptosis ,Biology ,Cell Line ,Mice ,Transduction, Genetic ,RAR-related orphan receptor gamma ,Gene expression ,medicine ,Animals ,Transcription factor ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Receptors, Thyroid Hormone ,Cell Differentiation ,Promoter ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,Molecular biology ,Tamoxifen ,medicine.anatomical_structure ,Gene Expression Regulation ,Receptors, Estrogen ,TCF Transcription Factors ,lcsh:RC581-607 ,Research Article - Abstract
BackgroundBasic helix-loop-helix E proteins are transcription factors that play crucial roles in T cell development by controlling thymocyte proliferation, differentiation and survival. E protein functions can be repressed by their naturally occurring inhibitors, Id proteins (Id1-4). Transgenic expression of Id1 blocks T cell development and causes massive apoptosis of developing thymocytes. However, the underlying mechanisms are not entirely understood due to relatively little knowledge of the target genes regulated by E proteins.ResultsWe designed a unique strategy to search for genes directly controlled by E proteins and found RORγt to be a top candidate. Using microarray analyses and reverse-transcriptase PCR assays, we showed that Id1 expression diminished RORγt mRNA levels in T cell lines and primary thymocytes while induction of E protein activity restored RORγt expression. E proteins were found to specifically bind to the promoter region of RORγt, suggesting their role in activating transcription of the gene. Functional significance of E protein-controlled RORγt expression was established based on the finding that RORγt rescued apoptosis caused by Id1 overexpression. Furthermore, expression of RORγt prevented Id1-induced p38 MAP kinase hyper-activation.ConclusionThese results suggest that E protein-dependent RORγt gene expression aids the survival of developing thymocytes, which provides a possible explanation for the massive apoptosis found in Id1 transgenic mice.
- Published
- 2008