NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE38354 Query DataSets for GSE38354
Status Public on Jun 01, 2012
Title Genome-Wide DNA Methylation Profiles in Hematopoietic Stem and Progenitor Cells Reveal Over-Representation of ETS Transcription Factor Binding Sites
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary DNA methylation is an essential epigenetic mark that is required for normal development. Knockout of the DNA methyltransferase enzymes in the mouse hematopoietic compartment reveals that methylation is critical for hematopoietic differentiation. To better understand the role of DNA methylation in hematopoiesis, we characterized genome-wide DNA methylation in primary mouse hematopoietic stem cells (HSC), common myeloid progenitors (CMP), and erythroblasts (ERY). Methyl Binding Domain protein 2 (MBD) enrichment of DNA followed by massively-parallel sequencing (MBD-Seq) was used to map genome-wide DNA methylation. Globally, DNA methylation was most abundant in HSC, with a 40% reduction in CMP, and 67% reduction in ERY. Only 3% of peaks arise during differentiation demonstrating a genome-wide decline in DNA methylation during erythroid development. Analysis of genomic features revealed that 98% of promoter CpG islands are hypomethylated, while 20-25% of non-promoter CpG islands are methylated. Proximal promoter sequences of expressed genes are hypomethylated in all cell types, while gene body methylation positively correlates with gene expression in HSC and CMP. Elevated genome-wide DNA methylation in HSC and the positive association between methylation and gene expression demonstrates that DNA methylation is a mark of cellular plasticity in HSC. Utilizing de novo motif discovery we identified overrepresented transcription factor consensus binding motifs in methylated sequences. Motifs for several ETS transcription factors, including GABPalpha and ELF1 are overrepresented in methylated regions. Our genome-wide survey demonstrates that DNA methylation is markedly altered during myeloid differentiation and identifies critical regions of the genome and transcription factor programs that contribute to hematopoiesis.
 
Overall design Examination of changes in methylation profiles during hematopoietic stem cell differentiation
 
Contributor(s) Hogart A, Lichtenberg J, Ajay SS, Anderson S, Margulies EH, Bodine DM
Citation(s) 22684279
Submission date May 31, 2012
Last update date May 15, 2019
Contact name Jens Lichtenberg
E-mail(s) lichtenbergj@mail.nih.gov
Phone 7402749495
Fax 3014024929
Organization name National Institutes of Health
Department National Human Genome Research Institute
Street address 49 Convent Dr 3A19
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL9185 Illumina Genome Analyzer (Mus musculus)
Samples (6)
GSM940569 Common Myeloid Progenitor MBD2-enriched
GSM940570 Erythroblast MBD2-enriched
GSM940571 Common Myeloid Progenitor supernatant
Relations
SRA SRP013455
BioProject PRJNA167810

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38354_RAW.tar 1.3 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap