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| Status |
Public on Feb 27, 2015 |
| Title |
NLRC5 specifically transactivates MHC class I and related genes through a distinctive SXY module |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
MHC class II (MHCII) genes are transactivated by the NOD-like receptor (NLR) factor CIITA, which is recruited to SXY regulatory modules of MHC promoters via a DNA-binding “enhanceosome” complex. NLRC5, another NLR protein, was recently found to control transcription of MHC class I (MHCI) genes. However, detailed understanding of its target-gene specificity and mechanism of action remained lacking. We therefore performed ChIP-sequencing experiments to gain comprehensive information on NLRC5-transactivated genes. In addition to classical MHCI genes, we identified novel NLRC5-targets exclusively in the H2-Q and H2-T regions of the MHCI locus, among which the best targets were found. Investigation of cells lacking the MHCII-enhanceosome factor RFX5 demonstrated its strict requirement for NLRC5 recruitment to the SXY module conserved in MHCI genes. Furthermore, patient-derived B cell lines deficient in RFX5, RFXAP, and RFXANK corroborated importance of the enhanceosome for MHCI transactivation. Although sharing similar SXY modules and common DNA-binding factors, CIITA and NLRC5 regulate distinct genes, as shown here using double-deficient Nlrc5-/-CIIta-/- mice. The identification of sequences occupied by NLRC5 in vivo allowed us to define a unique consensus motif for its recruitment, which diverges from that used by CIITA. Our results thus broaden our knowledge on transcriptional activity of NLRC5, highlighting its remarkable selectivity for genes encoding MHCI or related proteins and providing insights into the specificity of its recruitment.
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| Overall design |
Analysis of Nlrc5 binding sites in T-cells
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| Contributor(s) |
Ludigs K, Seguín-Estévez Q, Lemeille S, Ferrero I, Rota G, Chelbi S, Mattmann C, MacDonald HR, Reith W, Guarda G |
| Citation(s) |
25811463 |
| Submission date |
Jul 03, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Sylvain LEMEILLE |
| Organization name |
University of Geneva Medical School
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| Department |
Department of Pathology and Immunology
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| Street address |
1 rue Michel-Servet
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| City |
Geneva |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA254357 |
| SRA |
SRP044057 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59092_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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