Tag Archives: methylation

How does the soma to germline transfer work?

I never had problems to understand environmental induced sperm methylation as spermatozoa of animals are produced continuously by meiotic division.  But I learned that in humans all ova are produced before birth, so how could these ever be influenced by an environmental exposure? It seems that the dogma of prefabricated eggs is wrong as described already in 2012.

Rare mitotically active cells have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes

So there is a lifelong chance that environmental exposures both in fathers and mothers can be transmitted to the offspring “fat eggs, fat offspring” – there is no Weismann Barrier. (This remains also an important question as somatic gegen therapy could accidentally introduced germline changes – at least in theory).

But how does any soma to germline transfer work? A new paper examined this  in more detail. They found that the negative regulator of sperm activation in C elegans, SWM-1, is produced in body wall muscle, then secreted into the body cavity. Whenever it enters the gonad it finds it target TRY-5, a spermiogenesis activator, that influences sperm success.

So to the more conventional soma to germline theories of persistent methylation changes or RNA fragments ( as described in a recent review) there maybe more possibilities like microbiome transfer.

1, 2, 3

A new review [Allergy (2009) vol. 64 (3) pp. 348-353] examines the evidence that

(1) failure to up-regulate the interferon gamma (IFNg) response during infancy is an important determinant of the risk of allergic disease
(2) expression of the IFNg gene in naive T-cells is regulated by epigenetic mechanisms, and
(3) failure to up-regulate IFNg gene expression of naive T-cells associated with low early life microbial exposure.

If we replace “microbial exposure” with Continue reading 1, 2, 3

Asthma: a iatrogenic disease cont’d

I had already a thread here about asthma and iatrogenic factors last month including estrogens, vaccines, antibiotics, vitamin D, paracetamol, and Caesarean section. There may be even another kid on the block: folate. At least in mice in utero supplementation with methyl donors enhances allergic airway disease Continue reading Asthma: a iatrogenic disease cont’d

The epigenetic landscape

What I always feared, but couldn’t believe, is now confirmed by renowned experts in a new Cell editorial

Historically, the word “epigenetics” was used to describe events that could not be explained by genetic principles.

It goes back to Conrad Waddington – and describes now such bizarre and inexplicable features like paramutation in maize, position effetc variegation in Drosophila and methylation in humans. There is a nice analogy of the classical 1957 epigenetic landscape figure of Waddington where the course of the ball is influenced by hillls and valleys where it finally arrives – the Pinball arcade game

known factors that may regulate epigenetic phenomena are shown direcing the complex movements of pinballs (cells) across the elegant landscape … no specific order of molecular events is implied; as such a sequence remains unknown. Effector proteins recognize specific histone modifications…

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The first methylome available

-moblog- Having spent this weekend in Heidelberg city at a meeting of the German NGFN project I had the opportunity to listen to an excellent talk of Stephan Beck who works at the Wellcome Trust Sanger Center.

Epigenetics is the connecting link between the rather fixed genome and the variable transcriptome. To start with the end of the talk: Beck predicts for the near future highly parallel SNP, expression and methylation arrays. Although the first methylome has just been published 4 weeks ago by the Arabidopsis community (as with RNAi the plant people again at the forefront) there is still a long way ahead for a first human methylation map.

The latest information may be retrieved from www.epigenome.org, www.epigenome-noe.net, www.epitron.eu,
www.heroic-ip.eu and the German National Methylome Project on chromosome 21 (please google for the link). The methylome is largely an European initiative – the two US epigenome projects do not have any website so far. The network site has some introductory texts; Beck was also refering to a 2006 PLOS paper by Akhtar.

Currently there are 4 human chromosomes under work covering 873 genes (hopefully I captured this correctly as this was a very dense talk). 70% of genes examined so far are either clearly methylated or they are not methylated by testing 12 different tissues. Sperm stands out from all other tissues – which is not unexpected. Tissues originating from the same developmental background have similar methylation patterns – also not unexpected. A preliminary analysis of expression patterns shows that if the 5 prime end is methylated expression is suppressed- also not unexpected.

Fascinating: the colon cells that certainly have a close interaction with the environment do NEITHER show age NOR sex specific differences. Fascinating too: The most frequently methylated regions are ECRs (evolutionary conserved sequences) for whatever reason. Promotor methylation dips around the transcription start sites – from the plots I would say plus and minus 2000bp. Methylation seem to be also conserved between mouse and human tissues while methylation status seems stable over time.

Current bisulfite sequencing is still laborious, expensive and takes quite a long time while immunoprecipitation using MeDIP is getting an alternative. The Sanger people also did a study usinge Nimble(R) gene 50 mers where Ensembl and UCSC will soon have these data for display. Finally, methylation appears in blocks. TagMVPs (your guess is correct, these are tags for methylation variant profiles) construction is straightforward where the estimated 40 million CpG sites will probably be covered by less than 10 percent tagMVP – Haplo epi types are now called hepitypes, yea, yea.

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Addendum

Methyl Primer Express® Software – is a free software package to simplify and automate the primer design process in methylation experiments. The bisulfite kit is not free ;-)

Addendum

A new textbook and a nice preview