PGP:Epigenome

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Purpose

The genome is rich with both genes and cis-regulatory elements controlling the expression of various genes that define an individual. Mechanistically, many gene expression patterns are governed by more than simple regulatory sequences, and involve large epigenetic phenomena such as global repression, silencing, imprinting and X-inactivation. Even very local or seemingly random inactivation of autosomal genes may involve hereto unknown methylation (DNA or histone) mechanisms.


Most gene-specific changes are due to sequence-specific DNA-binding proteins. As such, the possibility exists that some genetic polymorphisms disrupt either the protein factors required for gene- or site=specific methylation patters or that they modify the methylation acceptor sites critical for gene expression or chromatin remodeling.


There are other efforts planned (Broad and elsewhere) to look that the individual variations in gene methylation patterns. While such variations will be much harder for making functional predictions, it may answer important questions such as epigenetic noise, tissue mosaicism and random inactivation of autosomes during development. PGP will undertake the examination of Phase One volunteers to examine these topics with our collaborators.

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