Gene body methylation and active gene expression - (Feb/28/2007 )
A new study published in Science reports that gene body methylation is associated with active expression of genes on the active X chromosome while their promoter remains unmethylated. There are previous reports showing that gene body methylation is associated if not required for active transcription. These findings raise a question: what is the role of gene body methylation, is it required for gene transcription? Are we going to have a "DNA methylation activation" apart from methylation silencing?
Any thoughts on this?
Hellman A, Chess A. Gene body-specific methylation on the active X chromosome. Science. 2007 Feb 23;315(5815):1141-3.
Abstract: Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific methylation of the inactive X chromosome has been demonstrated at promoter CpG islands, but the overall pattern of methylation on the active X(Xa) and inactive X (Xi) chromosomes is unknown. We performed allele-specific analysis of more than 1000 informative loci along the human X chromosome. The Xa displays more than two times as much allele-specific methylation as Xi. This methylation is concentrated at gene bodies, affecting multiple neighboring CpGs. Before X inactivation, all of these Xa gene body-methylated sites are biallelically methylated. Thus, a bipartite methylation-demethylation program results in Xa-specific hypomethylation at gene promoters and hypermethylation at gene bodies. These results suggest a relationship between global methylation and expression potentiality.
Hi pcrman,
sounds very interesting! I have seen some papers working on the methylation of specific exons - in the case I remember hypermethylation -> low expression. But during the last month there are also several reports on promoter specific hypermethylation leading to active expression. This may be due to silencing (there we are again) of repressor elements. I don't have my lap at hand, will post you the references later.
Krümel
damn, beaten to it.
we are seeing this also with our test systems and didn't know what to make of it.
It certainly is very interesting, all this methylation within the gene.
We saw this with our neocentromere system and stated that it maintained the overall chromatin state of the centromere (ie: heterochromatic) but seeing it on the active X is certainly interesting.
Must download the paper.
Nick
Hi Krümel,
Have you find the reference you mentioned. I'd like to have a look.
Like small RNA mediated gene expression regulation which is primarily regarded as a host defense mechanism and then evolved to be a general gene regulation mechanism in which there are both negative (RNAi) and positive (RNAa) regulation, DNA methylation is also a defense and gene regulation mechanism and positive regulation may be possible.
Hi pcrman,
I am in a little hurry - just two references:
(1) Dual role of DNA methylation for human Telomerase gene - Pubmed
(2) Hypermethylation of exon 1-7 of GR in rat hippocampus - Pubmed
Hope those are interesting 4U
Krümel
pcrman.
may this could be of interest to you also?
3' Methylation Paper
Nick
Isn't Igf2 regulated by methylation in a manner that hypermethylation causes expression?
I thought gene expression due to hypermethylation is widely known, although the opposite seems to be much more frequent... or am I mistaken?
Thus (as far as I know) the new finding here is: methylation in regions apart from the promoter region can regulate gene expression.
This seems quite likely to me, as methylation may well influence the 3D structure of the DNA, or its binding capabilities, for example.
Thus methylation in the actual gene may sterically hinder the gene from being expressed.
This (sort-of) goes in the direction of histone methylation.
Histones too can change the 3D Structure of the DNA by being modified ((un-)methylated, acetylated, etc.), and thus trigger/prevent expression.