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  1. Article ; Online: ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8

    Sin, Jun Hyung / Kashyap, Sujit / Acenas, Dante / Cortez, Jessica T / Lee, James / Marson, Alexander / Matloubian, Mehrdad / Waterfield, Michael R

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Volume 208, Issue 5, Page(s) 1155–1169

    Abstract: ... ...

    Abstract CD8
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Chromatin Immunoprecipitation ; DNA Transposable Elements/genetics ; Gene Deletion ; Gene Silencing ; Histones/genetics ; Humans ; Immunologic Memory/immunology ; Interleukin-2/biosynthesis ; Interleukin-2/metabolism ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Listeriosis/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Interleukin-7/biosynthesis ; Receptors, Interleukin-7/genetics ; Receptors, Interleukin-7/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
    Chemical Substances Atf7ip protein, mouse ; DNA Transposable Elements ; Histones ; Interleukin-2 ; Receptors, Interleukin-7 ; Repressor Proteins
    Language English
    Publishing date 2022-02-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2100996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Ikaros is a principal regulator of Aire

    Sin, Jun Hyung / Sucharov, Juliana / Kashyap, Sujit / Wang, Yi / Proekt, Irina / Liu, Xian / Parent, Audrey V / Gupta, Alexander / Kastner, Philippe / Chan, Susan / Gardner, James M / Ntranos, Vasilis / Miller, Corey N / Anderson, Mark S / Schjerven, Hilde / Waterfield, Michael R

    Science immunology

    2023  Volume 8, Issue 88, Page(s) eabq3109

    Abstract: Mutations in the gene encoding the zinc-finger transcription factor Ikaros ( ...

    Abstract Mutations in the gene encoding the zinc-finger transcription factor Ikaros (
    MeSH term(s) Humans ; Mice ; Animals ; Central Tolerance ; Cell Differentiation ; Thymus Gland ; Transcription Factors ; Gene Expression Regulation
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2023-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abq3109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Functional characterisation of ADP ribosylation factor-like protein 15 in rheumatoid arthritis synovial fibroblasts.

    Kashyap, Sujit / Kumar, Uma / Pandey, Anuj Kumar / Kanjilal, Maumita / Chattopadhyay, Patralika / Yadav, Chandrashekhar / Thelma, B K

    Clinical and experimental rheumatology

    2018  Volume 36, Issue 4, Page(s) 581–588

    Abstract: Objectives: ARL15 is a novel susceptibility gene identified in a recent GWAS in a north Indian rheumatoid arthritis (RA) cohort. However, the role of ARL15 or ARF family genes in RA aetiology remains unknown. Therefore, we aimed to i) establish the ... ...

    Abstract Objectives: ARL15 is a novel susceptibility gene identified in a recent GWAS in a north Indian rheumatoid arthritis (RA) cohort. However, the role of ARL15 or ARF family genes in RA aetiology remains unknown. Therefore, we aimed to i) establish the expression of ARL15 in rheumatoid arthritis synovial fibroblasts (RASF) and ii) its functional characterisation by assessing its effects on major inflammatory cytokines and interacting partners using a knockdown approach.
    Methods: RASF were cultured from synovial tissue obtained from RA patients (n=5) and osteoarthritis (OA) patients (n=3) serving as controls. Expression of ARL15, ARF1 and ARF6 in RASF was checked by semi-quantitative PCR and western blots; and altered expression of ARL15, if any, by induction of RASF with TNF using real-time PCR. The effect of ARL15 on the expression of adiponectin, adiponectin receptor I, IL6 and GAPDH and on cell mobility by invasion and migration assays were assessed by siRNA mediated gene knockdown.
    Results: Expression of ARL15, ARF1 and ARF6 was confirmed in RASF and OASF samples but ARL15 expression remained unaltered on TNF induction. Notably, ARL15 knockdown resulted in downregulation of IL6 and GAPDH, upregulation of adiponectin and adiponectin receptor I genes; and significant reduction in migration and invasion of RASF. Genemania showed significant interactions of ARL15 with genes responsible for insulin resistance and phospholipase D.
    Conclusions: This first report on ARL15 expression in RASF and its likely role in inflammation and metabolic syndromes through a TNF independent pathway, encourages hypothesis-free studies to identify additional pathways underlying RA disease biology.
    MeSH term(s) ADP-Ribosylation Factor 1/genetics ; ADP-Ribosylation Factors/genetics ; ADP-Ribosylation Factors/physiology ; Arthritis, Rheumatoid/etiology ; Arthritis, Rheumatoid/metabolism ; Fibroblasts/metabolism ; Humans ; Interleukin-6/genetics ; Synovial Membrane/metabolism
    Chemical Substances IL6 protein, human ; Interleukin-6 ; ADP-Ribosylation Factor 1 (EC 3.6.5.2) ; ADP-Ribosylation Factors (EC 3.6.5.2) ; ADP-ribosylation factor 6 (EC 3.6.5.2) ; ARL15 protein, human (EC 3.6.5.2)
    Language English
    Publishing date 2018-02-14
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A genome-wide association study reveals ARL15, a novel non-HLA susceptibility gene for rheumatoid arthritis in North Indians.

    Negi, Sapna / Juyal, Garima / Senapati, Sabyasachi / Prasad, Pushplata / Gupta, Aditi / Singh, Shalini / Kashyap, Sujit / Kumar, Ashok / Kumar, Uma / Gupta, Rajiva / Kaur, Satbir / Agrawal, Suraksha / Aggarwal, Amita / Ott, Jurg / Jain, Sanjay / Juyal, Ramesh C / Thelma, B K

    Arthritis and rheumatism

    2013  Volume 65, Issue 12, Page(s) 3026–3035

    Abstract: Objective: Genome-wide association studies (GWAS) and their subsequent meta-analyses have changed the landscape of genetics in rheumatoid arthritis (RA) by uncovering several novel genes. Such studies are heavily weighted by samples from Caucasian ... ...

    Abstract Objective: Genome-wide association studies (GWAS) and their subsequent meta-analyses have changed the landscape of genetics in rheumatoid arthritis (RA) by uncovering several novel genes. Such studies are heavily weighted by samples from Caucasian populations, but they explain only a small proportion of total heritability. Our previous studies in genetically distinct North Indian RA cohorts have demonstrated apparent allelic/genetic heterogeneity between North Indian and Western populations, warranting GWAS in non-European populations. We undertook this study to detect additional disease-associated loci that may be collectively important in the presence or absence of genes with a major effect.
    Methods: High-quality genotypes for >600,000 single-nucleotide polymorphisms (SNPs) in 706 RA patients and 761 controls from North India were generated in the discovery stage. Twelve SNPs showing suggestive association (P < 5 × 10(-5)) were then tested in an independent cohort of 927 RA patients and 1,148 controls. Additional disease-associated loci were determined using support vector machine (SVM) analyses. Fine-mapping of novel loci was performed by using imputation.
    Results: In addition to the expected association of the HLA locus with RA, we identified association with a novel intronic SNP of ARL15 (rs255758) on chromosome 5 (Pcombined = 6.57 × 10(-6); odds ratio 1.42). Genotype-phenotype correlation by assaying adiponectin levels demonstrated the functional significance of this novel gene in disease pathogenesis. SVM analysis confirmed this association along with that of a few more replication stage genes.
    Conclusion: In this first GWAS of RA among North Indians, ARL15 emerged as a novel genetic risk factor in addition to the classic HLA locus, which suggests that population-specific genetic loci as well as those shared between Asian and European populations contribute to RA etiology. Furthermore, our study reveals the potential of machine learning methods in unraveling gene-gene interactions using GWAS data.
    MeSH term(s) ADP-Ribosylation Factors/genetics ; Arthritis, Rheumatoid/genetics ; Asian Continental Ancestry Group/genetics ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide
    Chemical Substances ADP-Ribosylation Factors (EC 3.6.5.2) ; ARL15 protein, human (EC 3.6.5.2)
    Language English
    Publishing date 2013-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 127294-9
    ISSN 1529-0131 ; 0004-3591 ; 2326-5191
    ISSN (online) 1529-0131
    ISSN 0004-3591 ; 2326-5191
    DOI 10.1002/art.38110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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