title: Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project.
abstract: The Cd247 gene encodes for a transmembrane protein important for the expression and assembly of TCR/CD3 complex on the surface of T lymphocytes. Down-regulation of CD247 has functional consequences in systemic autoimmunity and has been shown to be associated with Type 1 Diabetes in NOD mouse. In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites, supported by histone marks and ChIP-seq data, that specifically have features of an enhancer and a promoter, respectively. We also identified a putative long non-coding RNA from the characteristically long first intron of the Cd247 gene. The long non-coding RNA annotation is supported by manual annotations from the GENCODE project in human and our expression quantification analysis performed in NOD and B6 mice using qRT-PCR. Furthermore, 17 of the 23 SNPs already known to be implicated with T1D were observed within the long non-coding RNA region in mouse. The spatially conserved regulatory elements identified in this study have the potential to enrich our understanding of the role of Cd247 gene in autoimmune diabetes.
authors.affiliation: Center for Non-coding RNA in Technology and Health, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark; IKVH, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Sachin
authors.initials: S
authors.lastname: Pundhir
authors.affiliation: ISIM Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen N, Denmark; EMV Immunology, BMC, Lund University, 221 84 Lund, Sweden.
authors.forename: Tine Dahlbæk
authors.initials: TD
authors.lastname: Hannibal
authors.affiliation: Center for Non-coding RNA in Technology and Health, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark; Herlev University Hospital, Department Pediatrics E, Arkaden, 2730 Herlev, Denmark.
authors.forename: Claus Heiner
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.affiliation: ISIM Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen N, Denmark.
authors.forename: Anne-Marie Karin
authors.initials: AM
authors.lastname: Wegener
authors.affiliation: Center for Non-coding RNA in Technology and Health, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark; Herlev University Hospital, Department Pediatrics E, Arkaden, 2730 Herlev, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.affiliation: ISIM Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen N, Denmark; EMV Immunology, BMC, Lund University, 221 84 Lund, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
authors.affiliation: Center for Non-coding RNA in Technology and Health, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark; IKVH, University of Copenhagen, Grønnegå̊rdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gorodkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017252:CD3 Complex / Q000235:genetics*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D062085:RNA, Long Noncoding; D014157:Transcription Factors
keywords: CD247; ENCODE; UCSC genome browser; cis-regulatory sequence; high-throughput sequencing; lncRNA