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DC Field | Value | Language |
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dc.citation.endPage | 109 | - |
dc.citation.startPage | 94 | - |
dc.citation.title | CELLULAR & MOLECULAR IMMUNOLOGY | - |
dc.citation.volume | 20 | - |
dc.contributor.author | Bae, Seyeon | - |
dc.contributor.author | Kim, Kibyeong | - |
dc.contributor.author | Kang, Keunsoo | - |
dc.contributor.author | Kim, Haemin | - |
dc.contributor.author | Lee, Minjoon | - |
dc.contributor.author | Oh, Brian | - |
dc.contributor.author | Kaneko, Kaichi | - |
dc.contributor.author | Ma, Sungkook | - |
dc.contributor.author | Choi, Jae Hoon | - |
dc.contributor.author | Kwak, Hojoong | - |
dc.contributor.author | Lee, Eun Young | - |
dc.contributor.author | Park, Sung Ho | - |
dc.contributor.author | Park-Min, Kyung-Hyun | - |
dc.date.accessioned | 2023-12-21T13:09:18Z | - |
dc.date.available | 2023-12-21T13:09:18Z | - |
dc.date.created | 2023-01-09 | - |
dc.date.issued | 2023-01 | - |
dc.description.abstract | Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-kappa B ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions. | - |
dc.identifier.bibliographicCitation | CELLULAR & MOLECULAR IMMUNOLOGY, v.20, pp.94 - 109 | - |
dc.identifier.doi | 10.1038/s41423-022-00959-x | - |
dc.identifier.issn | 1672-7681 | - |
dc.identifier.scopusid | 2-s2.0-85143885819 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/61333 | - |
dc.identifier.wosid | 000898603500001 | - |
dc.language | 영어 | - |
dc.publisher | CHIN SOCIETY IMMUNOLOGY | - |
dc.title | RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.relation.journalResearchArea | Immunology | - |
dc.type.docType | Article; Early Access | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | Osteoclasts | - |
dc.subject.keywordAuthor | super-enhancers | - |
dc.subject.keywordAuthor | enhancer RNAs | - |
dc.subject.keywordAuthor | Rheumatoid arthritis | - |
dc.subject.keywordPlus | SUPER-ENHANCERS | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTORS | - |
dc.subject.keywordPlus | RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | REGULATES OSTEOCLAST | - |
dc.subject.keywordPlus | CELL-DEVELOPMENT | - |
dc.subject.keywordPlus | B-ATF | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | NFATC1 | - |
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