Welcome to The Visible Embryo

Home- - -History-- -Bibliography- -Pregnancy Timeline- --Prescription Drugs in Pregnancy- -- Pregnancy Calculator- --Female Reproductive System- News Alerts -Contact

Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than ' million visitors each month.

WHO International Clinical Trials Registry Platform
The World Health Organization (WHO) has created a new Web site to help researchers, doctors and patients obtain reliable information on high-quality clinical trials. Now you can go to one website and search all registers to identify clinical trial research underway around the world!




Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System

Contact The Visible Embryo

News Alerts Archive

Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.
Content protected under a Creative Commons License.

No dirivative works may be made or used for commercial purposes.

Return To Top Of Page
Pregnancy Timeline by SemestersFemale Reproductive SystemFertilizationThe Appearance of SomitesFirst TrimesterSecond TrimesterThird TrimesterFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterDevelopmental Timeline
Click weeks 0 - 40 and follow fetal growth
Search artcles published since 2007

August 28, 2012--------News Archive Return to: News Alerts

Histone reshuffling plays an important role in regulating gene expression.

Illustration: Courtesy of Dr. Swami Venkatesh, Stowers Institute for Medical Research

WHO Child Growth Charts


ReadyGet SetRepress!

Scientists manipulate the Set2 pathway to show how genes are faithfully copied

The first step in gene expression is the exact copying
of a segment of DNA by the enzyme RNA polymerase II,
or pol II, into a mirror image RNA.

Scientists recognize that pol II does not transcribe RNA
via a smooth glide down the DNA highway,
but instead encounters an obstacle course
of DNA tightly wound around barrier proteins
called histones.

These histone proteins must be shoved aside
in order for pol II to transcribe RNA.

Previous work from the lab of Jerry Workman, Ph.D., an investigator at the Stowers Institute for Medical Research, showed how a protein associated with pol II - called Set2 - biochemically restored an inhibitory histone landscape after one round of transcription was completed, in order to prevent expression of potentially harmful RNA snippets.

Now in a study published in Aug. 22, 2012, advance online issue of Nature, his group uses yeast mutant in Set2 to reveal a surprising mechanism cells use to keep gene expression going—both in appropriate circumstances and inappropriate ones, as in cancer cells.

Workman: “The goal of my lab is to understand how transcription works. We knew that synthesis of an RNA strand must start at the beginning of a gene in order to code a full-length protein, and that it is essential to prevent RNA synthesis beginning at cryptic sites within a gene. In this study we addressed how that could happen at the molecular level.”

Two classes of chromatin remodeling factors
vie to activate or repress gene expression.

The “activators” pry histones from DNA
to allow the passage of pol II by decorating histones
with acetyl groups, which loosens their grip on DNA.

The opposing team, which includes Set2, then terminates
gene expression by planting their own biochemical flag,
this one a methyl group
which then attracts an enzyme to snip off the acetyl groups and restore chromatin to an inaccessible state.

This repression assures that erroneous initiation of transcription does not occur at a so-called
“cryptic” site within a gene.

Previously, many assumed that histones remain in contact with a DNA strand while they were decorated or stripped of acetyl groups by chromatin remodelers. “That was one possible scenario but we simply did not know what happened to histones on chromatin as the RNA strand elongated,” says Swami Venkatesh, Ph.D., a postdoctoral fellow in the Workman lab and the study’s first author. “We thought that some kind of exchange of histones took place during transcription but weren’t sure whether it happens over an entire gene.”

To investigate potential histone reshuffling, the group assessed chemical modification of histones in a form of a brewer’s yeast, Saccharomyces cerevisiae, and engineered it to track whether labeled histones moved in and out of chromatin. Using this system, they compared global acetylation and methylation of histones in all 6000 genes in both Set2 mutants and normal yeast.

They first observed that in normal cells the inhibitory methylation flag planted by Set2 spanned the trajectory of genes being expressed and that mark was, as anticipated, missing in Set2 mutants. In those mutants a large portion of genes showed a reciprocal increase in the acetylation mark, which could be explained by the loss of Set2’s recruitment of the acetyl snipper.

Further analysis revealed many of those acetylated histones had not in fact remained embedded in chromatin but had instead been “imported” from outside stores or as Venkatesh says, “pre-acetylated,” “This is important because it means that you don’t need to bring in a remodeling enzyme to re-acetylate histones,” he says.

These studies also reveal that Set2 plays a more complex role in controlling gene expression than anticipated. “The methyl mark placed on the histones by Set2 serves two functions,” explains Workman. “It not only recruits the de-acetylating enzyme that removes the acetyl marks from histones, but these new findings suggest it also prevents incorporation of pre-acetylated histones on the gene.”

The group also correlated these chemical modifications to aberrant gene expression using microarray analysis, which showed that unlike normal yeast, Set2 mutants produce variously truncated “cryptic” RNA transcripts.

“As genes are expressed, you do not want to shunt the system to produce RNAs that cannot be used,” says Venkatesh. “When cells undergo heat or environmental stress, they respond by making short RNAs encoding proteins that send a stress signal. Cells need Set2 under normal situations to keep these cryptic transcription start sites quiet.”

Workman agrees, noting that truncated
strands of RNA could possibly interfere
with translation of normal RNAs into protein.

“The fact that they are generated indicates chromosomal instability in the area encompassing these genes, a situation which can lead to cancer in humans,” he says. “The human counterpart of the Set2 protein, SETD2, reportedly functions as a tumor suppressor and its activity is lost in several types of cancers, including breast and renal carcinoma.”

Recognizing that histone exchange actually occurs over a large proportion is also relevant to cancer therapies in the pipeline. “Proteins that both acetylate and deacetylate histones are under investigation as targets of anti-cancer drugs,” says Venkatesh. “So it is very important to know how acetylated histones are brought to a gene. Mechanistic studies like ours provide this kind of insight.”

Also contributing to the paper were Michaela Smolle, Ph.D, Hua Li, Ph.D., and Madelaine Gogol—all of the Stowers—and Krishnamurthy Natarajan, Ph.D., Malika Saint, and Shambhu Kumar ofJawarharlal Nehru University in New Delhi.

This work was supported by the Stowers Institute for Medical Research and a grant from the National Institutes of General Medical Sciences (R01GM047867).

About the Stowers Institute for Medical Research
The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over 900 million dollars in pursuit of its mission.

Currently, the Institute is home to almost 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology-development and core facilities.

Original article: http://www.stowers.org/media/news/aug-22-2012