title: NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression.
abstract: Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive-immune responses. The promoters of MHC class I genes contain a well-conserved core module, the W/S-X-Y motif, which assembles a nucleoprotein complex termed MHC enhanceosome. A member of the nucleotide-binding domain, leucine-rich repeat (NLR) protein family, NLRC5, is a newly identified transcriptional regulator of MHC class I genes. NLRC5 associates with and transactivates the proximal promoters of MHC class I genes, although the molecular mechanism of transactivation has not been understood. In this article, we show that NLRC5-mediated MHC class I gene induction requires the W/S and X1, X2 cis-regulatory elements. The transcription factors RFX5, RFXAP, and RFXANK/B, which compose the RFX protein complex and associate with the X1 box, cooperate with NLRC5 for MHC class I expression. Coimmunoprecipitation experiments revealed that NLRC5 specifically interacts with the RFX subunit RFXANK/B via its ankyrin repeats. In addition, we show that NLRC5 can cooperate with ATF1 and the transcriptional coactivators CBP/p300 and general control nonderepressible 5, which display histone acetyltransferase activity. Taken together, our data suggest that NLRC5 participates in an MHC class I-specific enhanceosome, which assembles on the conserved W/S-X-Y core module of the MHC class I proximal promoters, including the RFX factor components and CREB/ATF1 family transcription factors, to promote MHC class I gene expression.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Torsten B
authors.initials: TB
authors.lastname: Meissner
authors.forename: Yuen-Joyce
authors.initials: YJ
authors.lastname: Liu
authors.forename: Kyoung-Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Amy
authors.initials: A
authors.lastname: Li
authors.forename: Amlan
authors.initials: A
authors.lastname: Biswas
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
mesh_terms: D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000502:physiology; D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: C531110:ATF1 protein, human; D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D015235:HLA-B Antigens; D047908:Intracellular Signaling Peptides and Proteins; C548042:NLRC5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors