Mitogen-induced transcriptional programming in human fibroblasts

Gene. 2021 Jul 15:145842. doi: 10.1016/j.gene.2021.145842. Online ahead of print.ABSTRACTTreatment of serum-starved quiescent human cells with fetal bovine serum (FBS), epidermal growth factor (EGF), or the phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) activates the RAS-MAPK pathway which initiates a transcriptional program which drives cells toward proliferation. Stimulation of the RAS-MAPK pathway activates mitogen- and stress-activated kinases (MSK) 1 and 2, which phosphorylate histone H3 at S10 (H3S10ph) or S28 (H3S28ph) (nucleosomal response) located at the regulatory regions of immediate-early genes, setting in motion a series of chromatin remodeling events that result in transcription initiation. To investigate immediate-early genes regulated by the MSK, we have completed transcriptome analyses (RNA sequencing) of human normal fibroblast cells (CCD-1070Sk) stimulated with EGF or TPA ± H89, a potent MSK/PKA inhibitor. The induction of many immediate-early genes was independent of MSK activity. However, the induction of immediate-early genes attenuated with H89 also had reduced induction with the PKA inhibitor, Rp-cAMPs. Several EGF-induced genes, coding for transcriptional repressors, were further upregulated with H89 but not with Rp-cAMPs, suggesting a role for MSK in modulating the induction level of these genes.PMID:34274479 | DOI:10.1016/j.gene.2021.145842

Source: Gene - July 18, 2021 Category: Genetics & Stem Cells Authors: Kiran L Sharma Shuo Jia Tasnim H Beacon Ifeoluwa Adewumi Camila L ópez Pingzhao Hu Wayne Xu James R Davie Source Type: research