J Autoimmun 2021 Jul 23;123:102709. Epub 2021 Jul 23.
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Switzerland; Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Rheumatology and Immunology, University Hospital Bern, Bern, Switzerland. Electronic address:
Chromatin remodeling, and a persistent histone 3 lysine 27 acetylation (H3K27ac) in particular, are associated with a sustained inflammatory response of synovial fibroblasts (SF) in rheumatoid arthritis (RA). Here we investigated individual functions of the writers of H3K27ac marks, the homologues histone acetyl transferases (HAT) CBP and p300, in controlling the constitutive and inflammatory gene expression in RA SF. We applied a silencing strategy, followed by RNA-sequencing and pathway analysis, complemented with the treatment of SF with inhibitors targeting the HAT (C646) or bromo domains (I-CBP) of CBP and p300. Read More