表达肾素的细胞是对于维持体内平衡至关重要的肌内分泌细胞。肾素受 cAMP、p300（组蛋白乙酰转移酶 p300）/CBP（CREB ​​结合蛋白）和 Brd4（含溴结构域蛋白 4）蛋白及相关途径调节。然而，抑制这些途径后发生的具体调控变化尚不清楚。我们用 3 种针对肾素转录所需的不同因子的抑制剂处理 As4.1 细胞（源自小鼠肾小球旁细胞的肿瘤细胞，组成型表达肾素）： 89-二盐酸盐，PKA（蛋白激酶A）抑制剂； JQ1、Brd4 溴结构域抑制剂；和 A-485、p300/CBP 抑制剂。我们进行了 ATAC-seq、单细胞 RNA 测序、CUT

Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.We treated As4.1 cells (tumoral cells derived from mouse juxtaglomerular cells that constitutively express renin) with 3 inhibitors that target different factors required for renin transcription: H-89-dihydrochloride, PKA (protein kinase A) inhibitor; JQ1, Brd4 bromodomain inhibitor; and A-485, p300/CBP inhibitor. We performed ATAC-seq, single-cell RNA sequencing, CUT&Tag, and chromatin immunoprecipitation sequencing for H3K27ac and p300 binding on biological replicates of treated and control As4.1 cells.In response to each inhibitor, Ren1 expression was significantly reduced and reversible upon washout. Chromatin accessibility at the Ren1 locus did not markedly change but was globally reduced at distal elements. Inhibition of PKA led to significant reductions in H3K27ac and p300 binding specifically within the Ren1 super-enhancer region. Further, we identified enriched TF (transcription factor) motifs shared across each inhibitory treatment. Finally, we identified a set of 9 genes with putative roles across each of the 3 renin regulatory pathways and observed that each displayed differentially accessible chromatin, gene expression, H3K27ac, and p300 binding at their respective loci.Inhibition of renin expression in cells that constitutively synthesize and release renin is regulated by an epigenetic switch from an active to poised state associated with decreased cell-cell communication and an epithelial-mesenchymal transition. This work highlights and helps define the factors necessary for renin cells to alternate between myoendocrine and contractile phenotypes.