Genome-wide DNA methylation profiling reveals distinct patterns during hematopoietic development

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHGRI	EPIGEN/TRANS/CHROM-3

Authors

• A Hogart
• J Lichtenberg
• S Ajay
• S Anderson
• E Margulies
• D Bodine

Abstract

Aberrant DNA methylation contributes to the pathogenesis of hematologic diseases including leukemia and myelodysplastic syndrome (MDS). Elucidating the pathways and genes regulated by DNA methylation during normal hematopoiesis may lead to improved therapies for disease. MBD2 protein-based pulldown combined with Illumina Solexa sequencing was used to survey alterations in DNA methylation during differentiation of hematopoietic stem cells (HSC), common myeloid progenitors (CMP), and lineage-committed erythroblasts (ERY) obtained from primary mouse tissue. Duplicate samples for each cell type were sequenced and peaks overlapping by at least 200 bp in each replicate were called. HSCs contained the highest level of DNA methylation with 85,797 peaks, CMP contained 50,638, and ERY had the most restricted pattern of methylation with only 27,839 peaks. Analysis of genomic distribution of DNA methylation peaks and in silico expression were compared and revealed that promoter methylation is anticorrelated to gene expression while gene body methylation is often positively associated with expression. Motif discovery was performed on methylated sequences and suggested that ETS family transcription factors are specifically altered by changes in DNA methylation. This study provides new insight into how DNA methylation contributes to cell-specific gene regulation.

back to top