TY - JOUR
T1 - 5-Hydroxymethylcytosine
T2 - A new kid on the epigenetic block?
AU - Matarese, Filomena
AU - Carrillo-De Santa Pau, Enrique
AU - Stunnenberg, Hendrik G.
N1 - Publisher Copyright:
Copyright © 2011 EMBO and Macmillan Publishers Limited.
PY - 2011
Y1 - 2011
N2 - The discovery of the Ten-Eleven-Translocation (TET) oxygenases that catalyze the hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) has triggered an avalanche of studies aiming to resolve the role of 5hmC in gene regulation if any. Hitherto, TET1 is reported to bind to CpG-island (CGI) and bivalent promoters in mouse embryonic stem cells, whereas binding at DNAseI hypersensitive sites (HS) had escaped previous analysis. Significant enrichment/accumulation of 5hmC but not 5mC can indeed be detected at bivalent promoters and at DNaseI-HS. Surprisingly, however, 5hmC is not detected or present at very low levels at CGI promoters notwithstanding the presence of TET1. Our meta-analysis of DNA methylation profiling points to potential issues with regard to the various methodologies that are part of the toolbox used to detect 5mC and 5hmC. Discrepancies between published studies and technical limitations prevent an unambiguous assignment of 5hmC as a 'true' epigenetic mark, that is, read and interpreted by other factors and/or as a transiently accumulating intermediary product of the conversion of 5mC to unmodified cytosines.
AB - The discovery of the Ten-Eleven-Translocation (TET) oxygenases that catalyze the hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) has triggered an avalanche of studies aiming to resolve the role of 5hmC in gene regulation if any. Hitherto, TET1 is reported to bind to CpG-island (CGI) and bivalent promoters in mouse embryonic stem cells, whereas binding at DNAseI hypersensitive sites (HS) had escaped previous analysis. Significant enrichment/accumulation of 5hmC but not 5mC can indeed be detected at bivalent promoters and at DNaseI-HS. Surprisingly, however, 5hmC is not detected or present at very low levels at CGI promoters notwithstanding the presence of TET1. Our meta-analysis of DNA methylation profiling points to potential issues with regard to the various methodologies that are part of the toolbox used to detect 5mC and 5hmC. Discrepancies between published studies and technical limitations prevent an unambiguous assignment of 5hmC as a 'true' epigenetic mark, that is, read and interpreted by other factors and/or as a transiently accumulating intermediary product of the conversion of 5mC to unmodified cytosines.
KW - 5-hydroxymethylcytosine
KW - 5-methylcytosine
KW - DNA demethylation
KW - sixth base
KW - Ten-Eleven-Translocation
UR - http://www.scopus.com/inward/record.url?scp=84858279865&partnerID=8YFLogxK
U2 - 10.1038/msb.2011.95
DO - 10.1038/msb.2011.95
M3 - Review article
C2 - 22186736
AN - SCOPUS:84858279865
SN - 1744-4292
VL - 7
JO - Molecular Systems Biology
JF - Molecular Systems Biology
IS - 1
M1 - 562
ER -