CREB regulates MHC class II expression in a CIITA-dependent manner

Carlos S. Moreno, Guy W. Beresford, Pascale Louis-Plence, Ann C. Morris, Jeremy M. Boss

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


The X2 box of MHC class II promoters is homologous to TRE/CRE elements and is required for expression of MHC class II genes. The X2 box-specific DNA binding activity, X2BP, was purified to homogeneity, sequenced, and identified as CREB. Transient transactivation experiments showed that CREB can cooperate with CIITA to enhance activation of transcription from MHC class II promoters in a dose-dependent manner. Binding of CREB to the class II promoter in vivo was demonstrated by a chromatin immunoprecipitation assay. Additionally, ICER, a dominant inhibitor of CREB function, was found to repress class II expression. These results demonstrate that CREB binds to the X2 box in vivo and cooperates with CIITA to direct MHC class II expression.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
Issue number2
StatePublished - Feb 1999

Bibliographical note

Funding Information:
We are indebted to R. Goodman for providing the RSV-CREBWT mammalian expression construct, M. Green for providing the ATF-1 and ATF-2 constructs, and P. Quinn for providing the pSG-ICER construct. We also thank C. Molina for providing ICER antisera, the laboratory of P. Farnham for the ChIP protocol, and M. Montminy for the PET-CREB bacterial expression construct. Peptide digests and internal amino acid microsequencing were performed under the direction of J. Pohl at the Emory Microchemical Facility, Winship Cancer Center, Emory University School of Medicine. Mass spectrometry analysis was performed under the direction of K. Stone at the W. M. Keck Foundation Biotechnology Resource Laboratory, Yale University. We thank C. Moran, G. Churchward, D. Pallas, P. Doetsch, and D. Reines for a critical reading of the manuscript. This work was supported by National Institutes of Health Grant GM43710 (J. M. B.). C. S. M. was supported by National Institutes of Health predoctoral fellowship AI09106.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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