Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Highly Accessed Research article

Euchromatin islands in large heterochromatin domains are enriched for CTCF binding and differentially DNA-methylated regions

Bo Wen14, Hao Wu2, Yuin-Han Loh3, Eirikur Briem1, George Q Daley3 and Andrew P Feinberg1*

Author Affiliations

1 Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

2 Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA

3 Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Howard Hughes Medical Institute, Boston, MA, USA

4 Current address: Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

For all author emails, please log on.

BMC Genomics 2012, 13:566  doi:10.1186/1471-2164-13-566

Published: 26 October 2012

Abstract

Background

The organization of higher order chromatin is an emerging epigenetic mechanism for understanding development and disease. We and others have previously observed dynamic changes during differentiation and oncogenesis in large heterochromatin domains such as Large Organized Chromatin K (lysine) modifications (LOCKs), of histone H3 lysine-9 dimethylation (H3K9me2) or other repressive histone posttranslational modifications. The microstructure of these regions has not previously been explored.

Results

We analyzed the genome-wide distribution of H3K9me2 in two human pluripotent stem cell lines and three differentiated cells lines. We identified > 2,500 small regions with very low H3K9me2 signals in the body of LOCKs, which were termed as euchromatin islands (EIs). EIs are 6.5-fold enriched for DNase I Hypersensitive Sites and 8-fold enriched for the binding of CTCF, the major organizer of higher-order chromatin. Furthermore, EIs are 2–6 fold enriched for differentially DNA-methylated regions associated with tissue types (T-DMRs), reprogramming (R-DMRs) and cancer (C-DMRs). Gene ontology (GO) analysis suggests that EI-associated genes are functionally related to organ system development, cell adhesion and cell differentiation.

Conclusions

We identify the existence of EIs as a finer layer of epigenomic architecture within large heterochromatin domains. Their enrichment for CTCF sites and DNAse hypersensitive sites, as well as association with DMRs, suggest that EIs play an important role in normal epigenomic architecture and its disruption in disease.

Keywords:
Epigenetics; H3K9me2; Euchromatin islands; CTCF; DNA methylation