Exploring the role of the epigenome in multiple sclerosis: a window onto cell-specific transcriptional potential.
The field of epigenomics involves the study of chromatin, the three dimensional complex of DNA, protein and non-coding RNAs that determines the accessibility of DNA by the transcriptional machinery. The epigenome varies from cell to cell and reflects the effect of external stimuli on cell fate and cell state. Thanks to emerging platforms and analysis methods, the systematic characterization of chromatin conformation throughout the genome has begun and has yielded several reference epigenome maps for a growing number of cell types. Such maps are enabling insights into the correlation architecture of different epigenomic marks: a number of discrete chromatin states are found across different cell types. The combination of these reference maps and robust platforms for genome-wide data generation has introduced a new era in which studies of human disease are becoming feasible. Little is known about the role of the epigenome in MS, but it is likely that, as in other inflammatory disease, susceptibility factors and events along the course of the disease will alter the chromatin state of different cell types in patients with MS. Here, we review different strategies for the characterization of the epigenome and how these strategies could be used to implement new studies to explore how alterations of chromatin architecture establish a dysregulated transcriptional state in the context of MS.
Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, NRB168, and Harvard Medical School, Boston, MA 02115, USA.
Anna
A
Kaliszewska
Philip L
PL
De Jager
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods / Q000639:trends; D044127:Epigenesis, Genetic / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics / Q000379:methods / Q000639:trends*; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000503:physiopathology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology
D005819:Genetic Markers