CG hypomethylation in Lsh-/- MEFs is associated with de novo H3K4me1 formation

Friday, November 08, 2013 — Poster Session III
10:00 a.m. – 12:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NCI	CHROM-10

Authors

W Yu
V Briones
R Lister
C McIntosh
Y Han
J Ren
M Terashima
E Lee
R Leighty
J.R Ecker
K Muegge

Abstract

DNA methylation is a major epigenetic mark and critical for normal mammalian development. To investigate if and how modulation of CG methylation affects cellular identity, we used primary murine embryonal fibroblasts (MEFs) and their derivative induced pluripotent stem (iPS) cells generated from mice with a deletion of Lsh. Using whole genome bisulfite sequencing for Lsh-/- MEFs, we report here about 30% reduction of DNA methylation compared to wild type MEFs. After reprogramming, Lsh-/- iPS cells show a higher predilection towards the neuron lineage indicating an altered cellular plasticity in cells with a CG hypomethylated genome. We provide evidence that H3K4me1 marks at neural lineage genes are linked to CG hypomethylation, are maintained through reprogramming, and are associated with enhancer activity and increased neural gene expression. Our data demonstrate that CG hypomethylation affects potential enhancer formation which can be preserved through reprogramming and influences the epigenetic memory for cellular plasticity.