Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes

被引：131

作者：

Ai, Rizi ^{[1
]}

Laragione, Teresina ^{[2
]}

Hammaker, Deepa ^{[3
]}

Boyle, David L. ^{[3
]}

Wildberg, Andre ^{[1
]}

Maeshima, Keisuke ^{[3
]}

Palescandolo, Emanuele ^{[4
]}

Krishna, Vinod ^{[4
]}

Pocalyko, David ^{[4
]}

Whitaker, John W. ^{[4
]}

Bai, Yuchen ^{[4
]}

Nagpal, Sunil ^{[4
]}

Bachman, Kurtis E. ^{[4
]}

Ainsworth, Richard I. ^{[1
]}

Wang, Mengchi ^{[1
]}

Ding, Bo ^{[1
]}

Gulko, Percio S. ^{[2
]}

Wang, Wei ^{[1
,5
]}

Firestein, Gary S. ^{[3
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA

[2] Icahn Sch Med Mt Sinai, Div Rheumatol, One Gustave L Levy Pl, New York, NY 10029 USA

[3] UCSD Sch Med, Div Rheumatol Allergy & Immunol, 9500 Gilman Dr, La Jolla, CA 92093 USA

[4] Janssen Pharmaceut, 1400 McKean Rd, Spring House, PA 19477 USA

[5] UCSD Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

DNA METHYLOME SIGNATURE; JOINT DESTRUCTION; AMERICAN-COLLEGE; CLASSIFICATION; METHYLATION; CHROMATIN; CRITERIA; OSTEOARTHRITIS; INVASIVENESS; ACTIVATION;

D O I：

10.1038/s41467-018-04310-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtininteracting protein-1 regulates FLS invasion into matrix. This work establishes a highresolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.

引用

页数：11

共 41 条

[1]

Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes [J].

Ai, Rizi ;

Hammaker, Deepa ;

Boyle, David L. ;

Morgan, Rachel ;

Walsh, Alice M. ;

Fan, Shicai ;

Firestein, Gary S. ;

Wang, Wei .

NATURE COMMUNICATIONS, 2016, 7

[2]

DNA Methylome Signature in Synoviocytes From Patients With Early Rheumatoid Arthritis Compared to Synoviocytes From Patients With Longstanding Rheumatoid Arthritis [J].

Ai, Rizi ;

Whitaker, John W. ;

Boyle, David L. ;

Tak, Paul Peter ;

Gerlag, Danielle M. ;

Wang, Wei ;

Firestein, Gary S. .

ARTHRITIS & RHEUMATOLOGY, 2015, 67 (07) :1978-1980

[3]

THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY CRITERIA FOR THE CLASSIFICATION AND REPORTING OF OSTEOARTHRITIS OF THE HIP [J].

ALTMAN, R ;

ALARCON, G ;

APPELROUTH, D ;

BLOCH, D ;

BORENSTEIN, D ;

BRANDT, K ;

BROWN, C ;

COOKE, TD ;

DANIEL, W ;

FELDMAN, D ;

GREENWALD, R ;

HOCHBERG, M ;

HOWELL, D ;

IKE, R ;

KAPILA, P ;

KAPLAN, D ;

KOOPMAN, W ;

MARINO, C ;

MCDONALD, E ;

MCSHANE, DJ ;

MEDSGER, T ;

MICHEL, B ;

MURPHY, WA ;

OSIAL, T ;

RAMSEYGOLDMAN, R ;

ROTHSCHILD, B ;

WOLFE, F .

ARTHRITIS AND RHEUMATISM, 1991, 34 (05) :505-514

[4]

DEVELOPMENT OF CRITERIA FOR THE CLASSIFICATION AND REPORTING OF OSTEOARTHRITIS - CLASSIFICATION OF OSTEOARTHRITIS OF THE KNEE [J].

ALTMAN, R ;

ASCH, E ;

BLOCH, D ;

BOLE, G ;

BORENSTEIN, D ;

BRANDT, K ;

CHRISTY, W ;

COOKE, TD ;

GREENWALD, R ;

HOCHBERG, M ;

HOWELL, D ;

KAPLAN, D ;

KOOPMAN, W ;

LONGLEY, S ;

MANKIN, H ;

MCSHANE, DJ ;

MEDSGER, T ;

MEENAN, R ;

MIKKELSEN, W ;

MOSKOWITZ, R ;

MURPHY, W ;

ROTHSCHILD, B ;

SEGAL, M ;

SOKOLOFF, L ;

WOLFE, F .

ARTHRITIS AND RHEUMATISM, 1986, 29 (08) :1039-1049

[5]

Synovial cellular and molecular markers in rheumatoid arthritis [J].

Amin, M. Asif ;

Fox, David A. ;

Ruth, Jeffrey H. .

SEMINARS IN IMMUNOPATHOLOGY, 2017, 39 (04) :385-393

[6]

Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts [J].

Araki, Yasuto ;

Wada, Takuma Tsuzuki ;

Aizaki, Yoshimi ;

Sato, Kojiro ;

Yokota, Kazuhiro ;

Fujimoto, Kenta ;

Kim, Yoon-Taek ;

Oda, Hiromi ;

Kurokawa, Riki ;

Mimura, Toshihide .

ARTHRITIS & RHEUMATOLOGY, 2016, 68 (05) :1111-1123

[7]

THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[8]

Apoptosis in rheumatoid arthritis [J].

Baier, A ;

Meineckel, I ;

Gay, S ;

Pap, T .

CURRENT OPINION IN RHEUMATOLOGY, 2003, 15 (03) :274-279

[9]

Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis [J].

Bartok, Beatrix ;

Firestein, Gary S. .

IMMUNOLOGICAL REVIEWS, 2010, 233 :233-255

[10]

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis [J].

Boyle, D. L. ;

Soma, K. ;

Hodge, J. ;

Kavanaugh, A. ;

Mandel, D. ;

Mease, P. ;

Shurmur, R. ;

Singhal, A. K. ;

Wei, N. ;

Rosengren, S. ;

Kaplan, I. ;

Krishnaswami, S. ;

Luo, Z. ;

Bradley, J. ;

Firestein, G. S. .

ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (06) :1311-1316

← 1 2 3 4 5 →