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CREB regulates MHC class II expression in a CIITA-dependent manner
C S Moreno1, G W Beresford, P Louis-Plence
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Immunity
|March 11, 1999
Summary
The study identifies CREB (cAMP response element-binding protein) as a key factor in MHC class II gene expression. CREB binds to the X2 box and works with CIITA to regulate these crucial immune genes.
Area of Science:
- Immunology
- Molecular Biology
- Gene Regulation
Background:
- MHC class II molecules are critical for immune responses.
- The X2 box in MHC class II promoters is essential for gene expression.
- The specific protein binding to the X2 box was previously unknown.
Purpose of the Study:
- To identify the DNA-binding protein that interacts with the X2 box of MHC class II promoters.
- To elucidate the role of this protein in the regulation of MHC class II gene expression.
- To investigate the interaction between this protein and CIITA (Class II Transactivator).
Main Methods:
- Purification and sequencing of the X2 box-binding protein (X2BP).
- Transient transactivation assays to assess the functional role of X2BP.
- Chromatin immunoprecipitation (ChIP) assay to confirm in vivo binding.
- Experiments using ICER (Inducible cAMP Early Repressor) to study inhibition.
Main Results:
- X2BP was identified as CREB (cAMP response element-binding protein).
- CREB binds to the X2 box of MHC class II promoters.
- CREB cooperates with CIITA to enhance MHC class II transcription in a dose-dependent manner.
- CREB binding to the promoter in vivo was confirmed by ChIP.
- ICER, an inhibitor of CREB, repressed MHC class II expression.
Conclusions:
- CREB is a crucial transcription factor that binds the X2 box in MHC class II promoters.
- CREB collaborates with CIITA to regulate MHC class II gene expression.
- This interaction is vital for directing the expression of MHC class II genes in vivo.