In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions.

摘要: The transcription factor NF-κB (NF-κB) plays a pivotal role in regulating inflammatory gene expression. Its effects are optimized by various coactivators including histone acetyltransferases (HATs) such as CBP/p300 and p/CAF. Evidence shows that high glucose (HG) conditions mimicking diabetes can activate the of NF-κB-regulated genes. However, underlying vivo nuclear chromatin remodeling events unknown. We therefore carried out immunoprecipitation (ChIP) assays monocytes to identify 1) factors bound promoters tumor necrosis factor-α (TNF-α) related genes under HG or diabetic conditions, 2) specific lysine (Lys (K)) residues on H3 (HH3) HH4 acetylated this process. treatment THP-1 increased transcriptional activity p65, which was augmented ChIP showed recruitment CPB, p/CAF TNF-α COX-2 promoters. Interestingly, also demonstrated concomitant acetylation HH3 at Lys9 Lys14, Lys5, Lys8, Lys12 Overexpression deacetylase (HDAC) isoforms inhibited p65-mediated transcription. In contrast, HDAC inhibitor stimulated acetylation. Finally, we human blood from type 1 2 subjects relative nondiabetic. These results show for first time increase HATs, well genes, leading