Genomic landscape of human allele-specific DNA methylation

Fang, F., Hodges, E., Molaro, A., Dean, M., Hannon, G. J., Smith, A. D. (2012) Genomic landscape of human allele-specific DNA methylation. Proceedings of the National Academy of Sciences of the United States of America, 109 (19). pp. 7332-7337. ISSN 00278424 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22523239
DOI: 10.1073/pnas.1201310109

Abstract

DNA methylation mediates imprinted gene expression by passing an epigenomic state across generations and differentially marking specific regulatory regions on maternal and paternal alleles. Imprinting has been tied to the evolution of the placenta in mammals and defects of imprinting have been associated with human diseases. Although recent advances in genome sequencing have revolutionized the study of DNA methylation, existing methylome data remain largely untapped in the study of imprinting. We present a statistical model to describe allele-specific methylation (ASM) in data from high-throughput short-read bisulfite sequencing. Simulation results indicate technical specifications of existing methylome data, such as read length and coverage, are sufficient for fullgenome ASM profiling based on our model. We used our model to analyze methylomes for a diverse set of human cell types, including cultured and uncultured differentiated cells, embryonic stem cells and induced pluripotent stem cells. Regions of ASM identified most consistently across methylomes are tightly connected with known imprinted genes and precisely delineate the boundaries of several known imprinting control regions. Predicted regions of ASM common to multiple cell types frequently mark noncoding RNA promoters and represent promising starting points for targeted validation. More generally, our model provides the analytical complement to cutting-edge experimental technologies for surveying ASM in specific cell types and across species.

Item Type: Paper
Uncontrolled Keywords: bisulfite untranslated RNA allele article cell culture DNA fingerprinting DNA methylation embryonic stem cell genome imprinting high throughput sequencing human human cell open reading frame pluripotent stem cell priority journal promoter region statistical model Algorithms Alleles Chromosomes, Human, X Cluster Analysis CpG Islands Embryonic Stem Cells Female Genome, Human Genomic Imprinting Humans Induced Pluripotent Stem Cells Male Models, Genetic
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Hannon lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date Deposited: 09 Jan 2013 16:07
Last Modified: 14 Oct 2015 15:52
PMCID: PMC3358917
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26417

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving