TY - JOUR
T1 - Epigenetic analysis in rheumatoid arthritis synoviocytes
AU - Ham, Seokjin
AU - Bae, Jae Bum
AU - Lee, Suman
AU - Kim, Bong Jo
AU - Han, Bok Ghee
AU - Kwok, Seung Ki
AU - Roh, Tae Young
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Rheumatoid arthritis (RA) is a complex chronic systematic disease with progressive destruction of the joints by invasive synoviocytes. To characterize the key regulators involved in the development of RA, we obtained multilayer epigenomics data including DNA methylation by whole-genome bisulfite sequencing, miRNA profiles, genetic variations by whole-exome sequencing, and mRNA profiles from synoviocytes of RA and osteoarthritis (OA) patients. The overall DNA methylation patterns were not much different between RA and OA, but 523 low-methylated regions (LMRs) were specific to RA. The LMRs were preferentially localized at the 5′ introns and overlapped with transcription factor binding motifs for GLI1, RUNX2, and TFAP2A/C. Single base-scale differentially methylated CpGs were linked with several networks related to wound response, tissue development, collagen fibril organization, and the TGF-β receptor signaling pathway. Further, the DNA methylation of 201 CpGs was significantly correlated with 27 expressed miRNA genes. Our interpretation of epigenomic data of the synoviocytes from RA and OA patients is an informative resource to further investigate regulatory elements and biomarkers responsible for the pathophysiology of RA and OA.
AB - Rheumatoid arthritis (RA) is a complex chronic systematic disease with progressive destruction of the joints by invasive synoviocytes. To characterize the key regulators involved in the development of RA, we obtained multilayer epigenomics data including DNA methylation by whole-genome bisulfite sequencing, miRNA profiles, genetic variations by whole-exome sequencing, and mRNA profiles from synoviocytes of RA and osteoarthritis (OA) patients. The overall DNA methylation patterns were not much different between RA and OA, but 523 low-methylated regions (LMRs) were specific to RA. The LMRs were preferentially localized at the 5′ introns and overlapped with transcription factor binding motifs for GLI1, RUNX2, and TFAP2A/C. Single base-scale differentially methylated CpGs were linked with several networks related to wound response, tissue development, collagen fibril organization, and the TGF-β receptor signaling pathway. Further, the DNA methylation of 201 CpGs was significantly correlated with 27 expressed miRNA genes. Our interpretation of epigenomic data of the synoviocytes from RA and OA patients is an informative resource to further investigate regulatory elements and biomarkers responsible for the pathophysiology of RA and OA.
UR - http://www.scopus.com/inward/record.url?scp=85064825438&partnerID=8YFLogxK
U2 - 10.1038/s12276-019-0215-5
DO - 10.1038/s12276-019-0215-5
M3 - Article
C2 - 30820026
AN - SCOPUS:85064825438
SN - 1226-3613
VL - 51
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
IS - 2
M1 - 22
ER -