Research article
Id1 induces apoptosis through inhibition of RORgammat expression
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* Corresponding author: Xiao-Hong Sun sunx@omrf.ouhsc.edu
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA
BMC Immunology 2008, 9:20 doi:10.1186/1471-2172-9-20
Published: 19 May 2008Abstract
Background
Basic 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.
Results
We 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.
Conclusion
These 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.