Download Interpreting the CpG island signal Rob Klose University of Oxford

S006
Interpreting the CpG island signal
Rob Klose
University of Oxford, Oxford, United Kingdom
In the mammalian genome most CpG dinucleotides are
methylated on the 5 position of cytosine and this epigenetically maintained DNA modification contributes to transcriptional
repression. An exception to this generally pervasive methylation
in normal tissues are short contiguous stretches of DNA that
have a high CpG content, called CpG islands (CGIs), which are
refractory to DNA methylation and found associated with up to
70% of human genes. Interestingly, abnormal methylation of
CGIs in cancer is often associated with gene silencing. Based
on these and other observations it has been proposed that CGIs
play an important role in gene regulatory element function but
how this is mechanistically achieved remains enigmatic. We
have recently made the important discovery that CGIs are specifically recognized by a class of chromatin modifying enzymes
that interpret the non-methylated CpG signal and translate this
into a unique chromatin environment at CGI elements. This
system appears to highlight gene regulatory elements in large
and complex vertebrate genomes, apparently making them
more accessible to gene regulatory factors. Using genome wide
profiling and new biochemical approaches we continue to dissect
how CGI chromatin impacts gene regulatory element function.