Promoter DNA methylation regulates progranulin expression and is altered in FTLD.

ABSTRACT:

Background

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of neurodegenerative diseases associated with personality changes and progressive dementia. Loss-of-function mutations in the growth factor progranulin (GRN) cause autosomal dominant FTLD, but so far the pathomechanism of sporadic FTLD is unclear.

Results

We analyzed whether DNA methylation in the GRN core promoter restricts GRN expression and, thus, might promote FTLD in the absence of GRN mutations. GRN expression in human lymphoblast cell lines is negatively correlated with methylation at several CpG units within the GRN promoter. Chronic treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) strongly induces GRN mRNA and protein levels. In a reporter assay, CpG methylati

SUBMITTER: Banzhaf-Strathmann J 

PROVIDER: S-EPMC3893557 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature