Reversing Mechanoinductive DSP Expression by CRISPR/dCas9-mediated Epigenome Editing.

ABSTRACT:

Rationale

DSP (desmoplakin), the most abundant component of desmosomes, which maintain the mechanical integrity of epithelium, is a genome-wide association study-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). Subjects with IPF express a significantly higher level of DSP than control subjects.

Objectives

Determine potential mechanisms by which DSP is regulated in lung fibrosis.

Methods

Matrigel-coated soft and stiff polyacrylamide gels were made to simulate the stiffness of normal and fibrotic lungs. Quantitative chromatin immunoprecipitation and electrophoretic mobility shift assay were used to evaluate transcription factor binding to the DSP promoter. Targeted DNA methylation was achieved by CRISPR (clustered regularly interspaced short p

SUBMITTER: Qu J 

PROVIDER: S-EPMC6118013 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature