Investigating The Roles Of DYRK1 And CBP/p300 Complex In Gene Transcription

DYRK1A,a dual specificity tyrosine-phosphorylation-regulated kinase 1A,is a dosage-dependent serine/threonine kinase,involved in both cytoplasmic and nuclear functions.Here,using proteomic analysis we identify two histone acetyltransferases,p300 and CBP,as interaction partners of DYRK1 A.As molecular mechanisms of how DYRK1 A regulates gene expression remains poorly understood,I study the function of DYRK1 A in nuclear.Using genome-wide location(ChIP-sequencing)analysis of DYRK1 A,we show that almost all the DYRK1 A peaks co-localize with p300 and CBP,at enhancers or near the Transcription start sites(TSS).Overexpression of DYKR1 A causes hyperphosphorylation of p300 and CBP.Modulation of DYRK1 A,by shRNA mediated reduction,leads to downregulation of expression of downstream located genes.Moreover,reduction in DYRK1 A by shRNA results in significant loss of H3K27 acetylation at these enhancers,suggesting that DYRK1 A modulates the activity of p300/CBP at these enhancers.I propose that DYRK1 A functions in enhancer regulation by interacting with p300/CBP and modulating their activity.Overall,our study identifies function of DYRK1 A at enhancers and provides new mechanistic understanding of DYRK1 A mediated regulation of gene expression,and may help better understand function of DYRK1 A in human pathologies.