Epic DNA methylation stress in childhood changes epigenetic's?

What?

What stress?  And what's epigenetic?

http://en.wikipedia.org/wiki/Epigenetic

The stress of gene expression change?

Could be.

OK then,  the STRESS of being a little punk?

I don't know...but after I read this i might. :)

http://www.the-scientist.com/blog/display/56139/
Early stress alters epigenome

Posted by Jef Akst
[Entry posted at 8th November 2009 06:00 PM GMT]

Scientists have figured out how stress experienced early in life can
cause long-lasting changes in physiology and behavior -- via
epigenetics.

Specifically, early stress appears to induce epigenetic changes in a
specific regulatory region of the genome, affecting the expression of
a hormone important in controlling mood and cognition into adulthood,
according to a study published online today (November 8) in Nature
Neuroscience.

This is the first study to depict a molecular mechanism by which
"stress early in life can cause effects that remain later in life,"
said epigeneticist Moshe Szyf of McGill University in Montreal. "This
can explain a lot of things that happen to us as humans and our
behavior later in life."

Stress endured early in life can influence the quality of physical and
mental health in adulthood, such as by causing hormonal alterations
associated with mood and cognitive disorders. But until now,
scientists did not understand the mechanism by which early life
experiences can produce such long-lasting effects.

According to a common hypothesis, the environment affects mental heath
by causing alterations to the physical properties of the genome that
influence gene expression -- the epigenome. Indeed, research suggests
that DNA methylation, one of the most intensely studied forms of
epigenetics, may explain why maternal care has a long-term influence
on behavior and hormones in rats.

To explore whether DNA methylation is behind the changes associated
with stress experienced early in life, molecular biologists Chris
Murgatroyd and Dietmar Spengler of the Max Planck Institute of
Psychiatry in Germany and colleagues examined the methylation patterns
of mice that were separated from their mothers for three hours a day
for the first ten days of their lives. Specifically, the researchers
looked for differences in the gene that encodes arginine vasopressin
(AVP), a hormone associated with mood and cognitive behaviors. The AVP
receptor is also a promising therapeutic target for stress-related
disorders.

From 6 weeks of age all the way up to 1 year, mice that experienced
early stress -- and showed the predicted behavioral and hormonal
differences -- also displayed significantly lower levels of
methylation in the regulatory region of the Avp gene in the brain.
This hypomethylation was specific to a subset of neurons in the
hypothalamic paraventricular nucleus -- a brain area involved in
regulating hormones linked to stress. These mice also had higher
levels of Avp mRNA, suggesting that lower methylation levels do indeed
affect hormone levels.

"Essentially the genome memorizes that [early life] stress," said
Szyf, who was not involved in the study. "Stress changes methylation,
and that stays the whole life."

The researchers further determined that the decreases in methylation
in stressed mice result from the inactivation of a protein known as
MeCP2, which is involved in the initial recruitment of proteins that
methylate the DNA.

The concept that social states in early life can affect health in
later life is "a completely revolutionary idea," Szyf said. This paper
provides a "detailed" molecular mechanism by which this can occur, and
"gives substance" to this theory.

Understanding the molecular details underlying this phenomenon is
essential to developing potential therapies for mental disorders that
stem from early adverse experiences, Murgatroyd added. "This has given
us new insight in how to possibly develop drugs for [these
illnesses]."

Treatments for reversing the effects of early life stress should begin
as early as possible, Spengler said. Reversing the inactivation of
MeCP2 might be possible, but "once [methylation] is laid down, you
cannot erase [it]," he said. "This is a mark that is very stable."
Treatments given later in life, then, must find ways to ameliorate the
phenotype, such as by blocking AVP receptors in animals with higher
AVP levels, he added.
<sniP>

----------

 MeCP2
http://en.wikipedia.org/wiki/MECP2
MECP2 (methyl CpG binding protein 2 (Rett syndrome)) is a gene[1] that
provides instructions for making its protein product, MECP2, also
referred to as MeCP2.[2] MECP2 appears to be essential for the normal
function of nerve cells. The protein seems to be particularly
important for mature nerve cells, where it is present in high levels.
The MeCP2 protein is likely to be involved in turning off
("repressing" or "silencing") several other genes. This prevents the
genes from making proteins when they are not needed. Recent work has
shown that MeCP2 can also activate other genes.[3] The MECP2 gene is
located on the long (q) arm of the X chromosome in band 28 ("Xq28"),
from base pair 152,808,110 to base pair 152,878,611.

DNA methylation is the major modification of eukaryotic genomes and
plays an essential role in mammalian development. Human proteins MECP2
(this protein), MBD1, MBD2, MBD3, and MBD4 comprise a family of
nuclear proteins related by the presence in each of a methyl-CpG
binding domain (MBD). Each of these proteins, with the exception of
MBD3, is capable of binding specifically to methylated DNA. MECP2,
MBD1 and MBD2 can also repress transcription from methylated gene
promoters. In contrast to other MBD family members, MECP2 is X-linked
and subject to X inactivation. MECP2 is dispensible in stem cells.
MECP2 gene mutations are the cause of some cases of Rett syndrome, a
progressive neurologic developmental disorder and one of the most
common causes of mental retardation in females.[4]
<snip-- but read the rest of this one for sure>

Mecp2 interacts with SKI protein:

http://en.wikipedia.org/wiki/SKI_protein
The Ski protein is a nuclear protooncoprotein that is associated with
tumors at high cellular concentrations.[1] Ski has been shown to
interfere with normal cellular functioning by both directly impeding
expression of certain genes inside the nucleus of the cell as well as
disrupting signaling proteins that activate genes.[2]

Ski negatively regulates transforming growth factor-beta (TGF-beta) by
directly interacting with Smads and repressing the transcription of
TGF-beta genes.[3] This has been associated with cancer due to the
large number of roles that peptide growth factors, of which TGF-beta
are a subfamily, play in regulating cellular functions such as cell
proliferation, apoptosis, specification, and developmental fate.[4]
<snip>

BINGO... another epic moment for psoriasis? We have to much TGF-beta
so we must have to little
ski protein????

Do we have retarded mecp2 genes?  But not retarded enough to become
morons or autistical?

Is that the true heartBREAK?

I'm gonna ski all winter long this year. I don't want to be a
moron with flaky skin. I want to ski on flakes of snow, you know?

No no not that ski dork OH...

Ok bye..

Thank you now we can hook up with p culprits like TGF-beta

http://en.wikipedia.org/wiki/TGF-beta

Wow.. if this is true we have another angle of attack on ALL
autoimmune conditions.

I'm blown away again. Like three times in only a few weeks. We had
segmented
filamentous bacterium (SFB) and GRP43 with the TLR4/LPS/MD-2 et al
problem and
what else?   Crikey can't think now. LOL

What's going on?

OK, relax randall... do tgf and get a griP.

Why? I already put the link right up above....

OK, so?

First, have i posted any mecp2 posts?

Yep, three times in our group:
http://groups.google.com/groups/search?hl=en&ie=UTF-8&q=mecp2+randall...

This is from one of those:

http://www.sciencedaily.com/releases/2006/11/061116121435.htm

[...]
RTT phenotype remains unclear. But the combination of anxious
behavior
and increased corticosterone release led McGill et al. to hypothesize
that their mice might be suffering from abnormal expression of Crh,
the
gene that produces corticotropin-releasing hormone (CRH). The authors
searched specific regions of the MeCP2308 mouse brain where CRH
normally works, and found that the mice do indeed overexpress Crh in
regions responsible for behavioral and physiological responses to
stress.

In healthy mammals, CRH activates the hypothalmic-pituitary-adrenal
axis in response to stressful events, stimulating glucocorticoid
release from the adrenal cortex. When the environmental stressor
subsides, glucocorticoid levels return to normal. Chronic stress,
however, can damage neurons, reduce synaptic plasticity, and impair
short-term memory -- as any stressed-out parent can attest.
<snip>

Susan is gonna be so PROUD of me... I found the gene that ties it all
together with HP endocrine glands and hormones..

Does Susan aPProve of me NOW.

I think so.

And guess what?

What?

Autism figures in and I"m not sure if glutathione is in this caper.

HOLY Shitzu it does.....

18 hits for glutathione and mecp2 on pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&...

The most recent::

www.ncbi.nlm.nih.gov/pubmed/16331260
Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b.
Suzuki M, Yamada T, Kihara-Negishi F, Sakurai T, Hara E, Tenen DG,
Hozumi N, Oikawa T.

Department of Cell Genetics, Sasaki Institute, Tokyo, Japan.

The Ets transcription factor PU.1 is a hematopoietic master regulator
essential for the development of myeloid and B-cell lineages. As we
previously reported, PU.1 sometimes represses transcription on forming
a complex with mSin3A-histone deacetyl transferase-MeCP2. Here, we
show an interaction between PU.1 and DNA methyltransferases, DNA
methyltransferase (Dnmt)3a and Dnmt3b (Dnmt3s). Glutathione-S-
transferase pulldown assay revealed that PU.1 directly interacted with
the ATRX domain of Dnmt3s through the ETS domain. Dnmt3s repressed the
transcriptional activity of PU.1 on a reporter construct with
trimerized PU.1-binding sites. The repression was recovered by
addition of 5-aza-deoxycitidine, a DNA methyltransferase inhibitor,
but not trichostatin A, a histone deacetylase inhibitor. Bisulfite
sequence analysis revealed that several CpG sites in the promoter
region neighboring the PU.1-binding sites were methylated when Dnmt3s
were coexpressed with PU.1. We also showed that the CpG sites in the
p16(INK4A) promoter were methylated by overexpression of PU.1 in
NIH3T3 cells, accompanied by a downregulation of p16(INK4A) gene
expression. These results suggest that PU.1 may downregulate its
target genes through an epigenetic modification such as DNA
methylation.

PMID: 16331260

What does the GST test prove?

I don't know...

What is it? LOL

http://en.wikipedia.org/wiki/Glutathione_S-transferase#GST-tags_and_t...

OH! Does it mean in this case that it's LOW or high?  Autism is LOW...
So let's go autistical and find out?

Si....

Is Mecp2 THE gene for autism?

Could be:
http://media.www.jhunewsletter.com/media/storage/paper932/news/2009/1...

[...]
MeCP2 is involved in turning off gene expression when not needed in
development. Degano and her colleagues believe that when MeCP2 doesn't
work, or when it works improperly, neurons first will not develop
their tips (which can become either dendrites or axons), and then
later will not form the necessary connections with other neurons due
to malfunctioning axon guidance. Both deficits are crippling to cells
that depend on proper connections for both survival and function.
<sniP>

mecp2 983 hits -- pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&...

137 of those contain the kicker *epigenetic* :
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&...

---------

Good lord... where does mecp2 show up in a Th1 and Th2 scale?

Wow... so blown away.

I better review:
http://en.wikipedia.org/wiki/Glutathione_S-transferase

Before i go ga ga.

=============================

Are you blown away?

Or insane in the membrane yet?

How about catching the flu?

Or the swine flu?

Yikes...

Pelosi’s Disastrous Health Care Plan
Posted by: Dr. Mercola ND
http://articles.mercola.com/sites/articles/archive/2009/11/07/Pelosis...

ARE FAT (Obese) people like autoimmune folks in the regards that some
trigger can make you FAT?
A Common Virus May Contribute to Obesity
Posted by: Dr. Mercola

http://articles.mercola.com/sites/articles/archive/2007/08/23/a-commo...
Scientists have found new evidence linking a common kind of viral
infection to obesity. The human adenovirus-36 (Ad-36) -- a cause of
respiratory infections and pinkeye -- may also be a contributing
factor to obesity, as it’s been found to transform adult stem cells
into fat cells, capable of storing additional fat.

Their findings were reported at the 234th national meeting and
exposition of the American Chemical Society in Boston, Massachusetts,
held August 19-23.

In a previous epidemiologic study, the researchers found that about 30
percent of obese people were infected with the Ad-36 virus, compared
to 11 percent of lean individuals. Exactly how the virus causes
obesity in people is still unknown, but it is believed that a specific
gene, called E4Orfl, in the virus may be the culprit that promotes the
obesity effect.

The team is now trying to figure out the factors that predispose some
people with the virus to develop obesity, whereas others remain
unaffected.
<sniP>

What does Dr. Mercola think?  Click the above link and see.

======================

OTOH dr. Brownstein says obesity is linked with lack of iodine for
your thyroid.

Which is a HPA cousin. Or so Susan would remind us.

You know your thyroid thingy.

277 hits for :: brownstein iodine
http://groups.google.com/groups/search?hl=en&qt_s=1&q=Brownstein+iodine

11 group hits for: brownstein iodine obesity
http://groups.google.com/groups/search?hl=en&q=Brownstein+iodine+obes...

==============

What else is heP with hpv these days?

Don't eat it. LOL

Doesn't this next link just show how smart our great...great biblical
grandparents were?

Heck yes...

1. HPV Causes Tonsil Cancer

A once-rare form of tonsil cancer caused by the same human papilloma
virus (HPV) that causes cervical cancer in women is spreading rapidly
though the United States.

Unlike other oral cancers, which often are caused by tobacco and/or
alcohol, the new cancer usually is spread through oral sex but can be
transmitted even through a kiss or a shared drinking glass. About 75
percent of its victims are men.

One study found that people who were infected with HPV were 32 times
more likely to develop the unusual cancer, which develops in the
tonsils or at the base of the tongue. The cancer was nine times more
common in men and women who had a total of at least six oral-sex
partners.

Oncologist Maura Gillison of the Ohio State University Medical Center
was one of the first researchers to recognize a connection between the
virus and tonsil cancer. After finding HPV in a substantial number of
throat tumors, she saw that the number of cancer cases had been rising
steadily starting with people born in 1935.

She realized the rise in numbers was connected with the change in
sexual behavior that began in the 1950s and 1960s. People began to
have more sexual partners, and a virus that was once rare began to
quietly spread.

Gillison believes cases of  HPV tonsil cancer are increasing by 5
percent each year, and experts worry that the virus could spread and
cause a spike in cancer cases. Gillison believes a solution might be
to vaccinate all boys, as well as girls, against the HPV virus.

An FDA advisory committee recently recommended the HPV vaccine
Gardasil be approved for young males to prevent genital warts. But
some experts disagree, pointing to the numerous side effects,
including death, linked to the vaccine, as well as its high cost
(three doses at $120 each over a period of six months) for a series of
shots. Gardasil was approved in 2006 for girls.

Tonsil cancer isn’t as deadly as other forms of throat cancer because
HPV-caused throat cancers respond better to surgery and radiation.
Still, rates are rising, and if the trend continues, more oral cancers
will be caused by HPV than tobacco or alcohol within 10 years, Gillian
said.

Even at today’s rates, the statistics are still surprising: Half as
many people get oral cancer each year that is caused by HPV as those
who develop cervical cancer.
<sniP>

So get your tonsils out early if your a swinger.

And if you swing with P you might not need it.

Why is that?

Because your mecp2 level's are low anyway and your not gonna get
cancer due to that fact.

Why?

I don't know... it's what i interpret from this stuff.

You want to fall orally in love with the most popular aPPle pie in
town is your business and not mine.  <w>

-------------

Oh wait. Did i forget this?

http://en.wikipedia.org/wiki/PU.1
Transcription factor PU.1 is a protein that in humans is encoded by
the SPI1 gene.[1]

This gene encodes an ETS-domain transcription factor that activates
gene expression during myeloid and B-lymphoid cell development. The
nuclear protein binds to a purine-rich sequence known as the PU-box
found near the promoters of target genes, and regulates their
expression in coordination with other transcription factors and
cofactors. The protein can also regulate alternative splicing of
target genes. Multiple transcript variants encoding different isoforms
have been found for this gene.[2]

Interactions
SPI1 has been shown to interact with NONO,[3] GATA2,[4] FUS[5] and
IRF4.[6][7]

=============

Is this another randall epic revelation or what?

Yes... and in spades. NONO, GATA, IRF4 and FUS....

Must not make a fus...

But over 60 hits for randall NO NO
http://groups.google.com/groups/search?hl=en&ie=UTF-8&q=nono+randall+...

Wrong NO NO mister ga ga... LOLO

And over 30 hits for randall gata (but for gata-3 and not gata-2)
http://groups.google.com/groups/search?hl=en&ie=UTF-8&q=gata+randall+...

So gata-2 moves us even futher upstream?

Let's look:

http://en.wikipedia.org/wiki/GATA2
GATA binding protein 2, also known as GATA2, is a human gene. The
protein encoded by this gene is a transcription factor.[1]

The GATA family of transcription factors, which contain zinc fingers
in their DNA binding domain, have emerged as candidate regulators of
gene expression in hematopoietic cells.[2] GATA1 is essential for
normal primitive and definitive erythropoiesis and is expressed at
high levels in erythroid cells, mast cells, and megakaryocytes. GATA2
is expressed in hematopoietic progenitors, including early erythroid
cells, mast cells, and megakaryocytes, and also in nonhematopoietic
embryonic stem cells. In chicken erythroid progenitors, forced
expression of GATA2 promotes proliferation at the expense of
differentiation.[3] GATA3 expression is restricted to T-lymphoid cells
and some nonhematopoietic cell types, including embryonic stem cells.
[4]

Interactions
GATA2 has been shown to interact with Pituitary-specific positive
transcription factor 1,[5] HDAC3,[6] Zinc finger and BTB domain-
containing protein 16,[7] LMO2,[8] Promyelocytic leukemia protein[9]
and SPI1.[10]
<sniP>

Well?

Gata-2 does bring sPi1 in to this thing?

http://en.wikipedia.org/wiki/SPI1

And the NONO protein:

http://en.wikipedia.org/wiki/NONO
Non-POU domain-containing octamer-binding protein is a protein that in
humans is encoded by the NONO gene.[1][2][3]

 Interactions
NONO has been shown to interact with SFPQ,[4] SPI1[5] and Androgen
receptor.[6]
<sniP>

For non pou i get 1128 hits on pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&...

For non pou with the kicker NONO i only get 7 hits:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&...

While all or most of my hits are for nitrogen o

Certainly it's all becoming CLEARer and so shall WE.