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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 one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal 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 HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Aug 16, 2013


eRNA model

A new hierarchical model for enhancer function has been proposed by a collaboration between the University of California, San Diego and the University of Eastern Finland.

Knowing more about how enhancers may provide more access to gene regulation.

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eRNAs may provide new avenues for gene therapy

A study investigating the function of the newly discovered enhancer RNA molecules (eRNAs), may open new avenues for gene therapy. Altering the production and function of these molecules could affect the expression of genes and as a consequence, possibly alter the progression of various diseases.

Published in the prestigious Molecular Cell on 8 August, the study was carried out by collaboration between the University of California, San Diego and the University of Eastern Finland.

Promoters are located at the beginning of genes. But gene expression is also regulated by enhancers; and, enhancers can be located thousands of base pairs away from the gene they regulate.

Enhancers are responsible for cell-specific gene regulation, and it had been thought that their number was static within the differentiated cell they inhabit. But studies, beginning in 2010, revealed that non-coding RNA molecules are also being produced in enhancer regions. However, no study until now, has identified the functional importance of enhancer RNAs (eRNAs).

In the current study researchers demonstrate that enhancer regions progress from TLR4 loosening of histone binding which allows transcription factor remodeling (minutes in duration), then onto histone acetylation (minutes in duration) and eRNA transcription (minutes to hours in duration), finally to dimethylation of histone H3 lysine 4 (H3K4me1/2).

H3K4me1and H3K4me2 histone modifiiers are used to identify the location of enhancer regions on DNA as they boost gene transcription.

Enhancer transcription causes long-term epigenetic changes in cells.

Besides offering valuable insight into the function of this novel type of RNA, the researchers believe their findings will open new avenues for treatments targeting enhancer sequences — which may lead to alteration of gene expression. In June, this same group published a study in Nature, reporting the first time reduction in target gene expression using eRNA knockdowns.

Molecular Cell Summary
Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell-type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ∼3,000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4, and Mll3 and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts.

Nature 498, 511–515 (27 June 2013) doi:10.1038/nature12209
Rev-Erb-α and Rev-Erb-β are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm1, 2, metabolism3, 4 and inflammatory responses5. Rev-Erbs function as transcriptional repressors by recruiting nuclear receptor co-repressor (NCoR)–HDAC3 complexes to Rev-Erb response elements in enhancers and promoters of target genes6, 7, 8, but the molecular basis for cell-specific programs of repression is not known. Here we present evidence that in mouse macrophages Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage-lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby messenger RNAs, suggesting a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a modified form of global run-on sequencing that quantifies nascent 5′ ends, we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription-factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for a direct role of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription.

Postdoctoral Researcher Minna U. Kaikkonen at A.I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland was one of the two lead authors of the current study, carried out under Professor Christopher Glass. Dr Kaikkonen completed her post doc study in Professor Glass' research group at the University of California, San Diego in 2009. Besides Dr Kaikkonen, the UEF contributors to the earlier study from June also include Postdoctoral Researcher Hanna P. Lesch.

The main funders of the study are Fondation Leducq, Sigrid Jusélius Foundation, the Academy of Finland, ASLA Fulbright, the Finnish Foundation for Cardiovascular Research, the Finnish Cultural Foundation (North Savo Regional Fund), Orion-Farmos Research Foundation and the US National Institutes of Health grants DK091183, CA17390, and DK063491.

For further information, please contact: Postdoctoral Researcher Minna Kaikkonen, minna.kaikkonen(at)uef.fi or Professor Christopher Glass ckg(at)csd.edu

Research article in Molecular Cell:
Kaikkonen MU, Spann N, Heinz S, Romanoski CE, Allison KA, Stender JD, Chun HB, Tough DF, Prinjha RK, Benner C and Glass CK. Remodeling of the enhancer landscape during macrophage activation is linked to enhancer transcription. Molecular cell, 2013; Volume 51, Issue 3, 310-325


Research article in Nature:
Lam MTY, Cho H, Lesch HP, Heinz S, Tanaka-Oishi Y, Benner C, Kaikkonen MU, Salim A, Kosaka M, Lee CY, Watt A, Grossman T, Rosenfeld MG, Evans RM, Glass CK. Rev-Erbs negatively regulate macrophage gene expression by repressing enhancer-directed transcription. Nature 2013 Jun 27; 498(7455):511-5 http://www.nature.com/nature/journal/v498/n7455/full/nature12209.html

Original press release: http://www.wistar.org/news-and-media/press-releases/wistar-scientists-decipher-structure-nata-enzyme-complex-modifies-most