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Series GSE59092 Query DataSets for GSE59092
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
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.
Overall design Analysis of Nlrc5 binding sites in T-cells
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
Department Department of Pathology and Immunology
Street address 1 rue Michel-Servet
City Geneva
ZIP/Postal code 1211
Country Switzerland
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (9)
GSM1427342 A_WT
GSM1427343 B_WT
GSM1427344 C_WT
BioProject PRJNA254357
SRA SRP044057

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Supplementary file Size Download File type/resource
GSE59092_RAW.tar 1.3 Gb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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