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Mianesaz, H.* ; Göczi, L.* ; Bojcsuk, D.* ; Ghalamkari, S.* ; Fadel, L. ; Póliska, S.* ; Penyige, A.* ; Nagy, L.* ; Nagy, G.* ; Vámosi, G.* ; Széles, L.*

Genome-wide chromatin profiling reveals a non-limiting role for RXR in macrophage-like cells stimulated with multiple nuclear receptor agonists.

J. Biol. Chem.:111486 (2026)
Postprint Forschungsdaten DOI PMC
Open Access Green
Retinoid X receptor (RXR) is an obligate heterodimerization partner for many nuclear receptors. In the absence of ligands, RXR occupies thousands of genomic regions, with its binding landscape predominantly determined by cell identity. In the presence of agonists of RXR or its partners, RXR occupancy is changed at a subset of binding regions. The characteristics of these ligand-responsive binding regions remain largely unexplored. We used ChIP-seq to profile RXR occupancy in PMA-differentiated THP-1 cells treated with agonists of RXR or partner receptors, including RARα, VDR, PPARδ, PPARγ, LXRs, and TR, or a 'cocktail' containing multiple agonists. The RXR agonist LG268 produced a stronger increase in RXR occupancy than any of the six partner-receptor agonists or their combination. The relevance of ligand-induced RXR peaks was confirmed by analyses of motif enrichment and RXR occupancy at regulatory elements of target genes. RXR binding was investigated in more detail in cells treated with the VDR agonist, calcitriol. Calcitriol markedly enhanced VDR binding, but the corresponding increase in RXR occupancy was less pronounced. We found that both ligand-induced and unresponsive RXR peaks were involved in gene regulation, and only a small subset (∼3%) of calcitriol-regulated genes exhibited decreases in both RXR binding and mRNA levels in response to combined agonist treatment. These results support a model in which RXR functions as a non-limiting module in a macrophage-like cell type, and interference between pathways is minimally attributable to RXR sequestration.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chip‐sequencing (chip‐seq) ; Macrophage ; Nuclear Receptor ; Retinoid X Receptor (rxr) ; Transcription Factor ; Transcriptomics ; Vitamin D Receptor (vdr)
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: 111486 Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Endocrinology (IDE)