The MHC-specific enhanceosome and its role in MHC class I and beta(2)-microglobulin gene transactivation.
The promoter regions of MHC class I and beta(2)-microglobulin (beta(2)m) genes possess a regulatory module consisting of S, X, and Y boxes, which is shared by MHC class II and its accessory genes. In this study we show that, similar to MHC class II, the SXY module in MHC class I and beta(2)m promoters is cooperatively bound by a multiprotein complex containing regulatory factor X, CREB/activating transcription factor, and nuclear factor Y. Together with the coactivator class II transactivator this multiprotein complex drives transactivation of these genes. In contrast to MHC class II, the multiprotein complex has an additional function in the constitutive transactivation of MHC class I and beta(2)m genes. The requirement for all transcription factors in the complex and correct spacing of the binding sites within the SXY regulatory module for complex formation and functioning of this multiprotein complex strongly suggests that this complex can be regarded as a bona fide enhanceosome. The general coactivators CREB binding protein, p300, general control nonderepressible-5, and p300/CREB binding protein-associated factor exert an ancillary function in MHC class I and beta(2)m transactivation, but exclusively through the class II transactivator component of this enhanceosome. Thus, the SXY module is the basis for a specific enhanceosome important for the constitutive and inducible transactivation of MHC class I and beta(2)m genes.
Gobin
S J
SJ
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. gobin@LUMC.nl
van Zutphen
M
M
Westerheide
S D
SD
Boss
J M
JM
van den Elsen
P J
PJ
D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005805:Genes, MHC Class I; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D001613:beta 2-Microglobulin