Project name: Homo sapiens

Description: The multifunctional scaffolding protein β-arrestin-1 plays a vital role in mediating the proliferative effects of nicotine through nAChR signaling. β-arrestins were initially known as negative regulators of GPCR mediated signaling as they promote internalization and desensitization of GPCRs. However, new roles of β-arrestins in receptor trafficking and signaling have been discovered in recent years. They are known to regulate signaling through a number of receptors such as Notch, endothelin A receptor, frizzled, smoothened and the nicotinic cholinergic receptors. Studies from our lab revealed that nAChR signaling induces the translocation of β-arrestin-1 to the nucleus, in a Src dependent manner, where it directly binds to the proliferative E2Fs. Furthermore, the nuclear translocation of β-arrestin-1 results in recruitment of p300 to E2F1 regulated proliferative promoters facilitating histone acetylation and transcription of these promoters. Given the role of β-arrestin-1 in nicotine induced gene expression, we attempted to explore the global association of β-arrestin-1 to the genomic regions upon nicotine stimulation by ChIP sequencing. It was found that β-arrestin-1 is recruited on the promoters of many genes that regulate EMT as well as other regulatory pathways. In this assay, β-arrestin-1 was found to be associated with the promoter regions of genes such as ZNF768, ZNF131, CSF3R, HMGA2, TAL1, RCC1, NKX2-4 etc in response to nicotine stimulation.Overall design: Serum starved/quiescent A549 cells and Nicotine stimulated A549 cells

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2012-09-07