11.07.2015 Views

Novel genetic and epigenetic alterations in ... - Ous-research.no

Novel genetic and epigenetic alterations in ... - Ous-research.no

Novel genetic and epigenetic alterations in ... - Ous-research.no

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Introductionmethylation dur<strong>in</strong>g embryogenesis, <strong>and</strong> by such establish <strong>no</strong>vel methylation marks on theDNA[8;26]. Some genes, <strong>in</strong>clud<strong>in</strong>g impr<strong>in</strong>ted genes, are <strong>in</strong>herited via the germ l<strong>in</strong>e[27;28].How epi<strong>genetic</strong> <strong>in</strong>formation can be passed via germ cells is still unclear as a substantialepi<strong>genetic</strong> re-programm<strong>in</strong>g takes place dur<strong>in</strong>g early embryogenesis, often thought of as anerasure of methylation marks.Promoter hypermethylation impair gene expression by prevent<strong>in</strong>g transcription factors tob<strong>in</strong>d to DNA. This occurs <strong>in</strong> two ways, either by direct <strong>in</strong>hibition of the b<strong>in</strong>d<strong>in</strong>g oftranscription factors to the methylated sequence[29;30], or via recruitment of prote<strong>in</strong>s with amethyl b<strong>in</strong>d<strong>in</strong>g doma<strong>in</strong> (MBD prote<strong>in</strong> family) which leads to condensation of the chromat<strong>in</strong>structure by the means of histone deacetylation (reviewed <strong>in</strong> [31])(Figure 3). K<strong>no</strong>ck<strong>in</strong>g outMBD-prote<strong>in</strong>s with RNA <strong>in</strong>terference re-<strong>in</strong>troduces transcription of <strong>in</strong>itially <strong>in</strong>active geneswithout alter<strong>in</strong>g the methylation status, thereby clearly demonstrat<strong>in</strong>g the role of MBDs as al<strong>in</strong>k between promoter hypermethylation <strong>and</strong> gene expression[32]. Still, the role of mutations<strong>in</strong> either of the MBD genes are unclear[33;34].16

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!