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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 12, 2013

 

components of the human genome

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HSCI expands human genome map with epigenetics

Ten years ago, scientists announced the end of the Human Genome Project, the international attempt to learn which combination of four nucleotides—adenine, thymine, cytosine, and guanine—is unique to homo sapien DNA. Now they are adding the study of epigenetics.

The biological alphabet helped researchers identify the approximately 25,000 genes coded in the human genome, but as time went on, questions arose about how all of these genes are controlled. Now, Harvard Stem Cell Institute Principal Faculty member Alexander Meissner, PhD, reports another milestone, this time contributing to the multilayered NIH-funded human Roadmap Epigenomics Project.


Epigenetics is the study of how the over 200 human cell types (e.g., muscle cells, nerve cells, liver cells, etc.) can have an identical compliment of genes but express them differently. Part of the answer lies in the way that DNA is packaged, with tight areas silencing genes and open areas allowing for genes to be translated into proteins. Stem cells differentiate into various cell types by marking specific genes that will be open and closed after division.


New research by Meissner, published online as a letter in the journal Nature, describes the dynamics of DNA methylation across a wide range of human cell types. Chemically, these marks are the addition of a methyl group—one carbon atom surrounded by three hydrogen atoms (CH3)—anywhere a cytosine nucleotide sits next to a guanine nucleotide in the DNA sequence.

Meissner's team, led by graduate student Michael Ziller, at Harvard's Department of Stem Cell and Regenerative Biology mapped nearly all of the 28-million cytosine-guanine pairings among the 3-billion nucleotides that make up human DNA, and then wanted to know which of these 28 million are dynamic or static across all the cell types.


The researchers found that eighty percent of the 28-million cytosine-guanine pairs are largely unchanged and might not participate in the regulation of the cell types, while the dynamic ones sit at sites that are relevant for gene expression—in particular distal regulatory sites such as enhancers.


Said Meissner: "When we asked, how many of them are changing, the answer was a very small fraction. Importantly this allows us to improve our current approaches of mapping this important mark through more targeted strategies that still capture most of the dynamics."

The methylation map generated by the Meissner lab is part of a larger National Institutes of Health (NIH) consortium to look at all of the different epigenetic modification that are found across a large number of human cell and tissue types.


Earlier this year, the Meissner's lab recorded all of the gene expression and multi-layered epigenetic dynamics that take place in early stem cell differentiation when they prepare to divide into their next fated cell type.


In addition to his roles at Harvard, Meissner is affiliated with the Broad Institute and the New York Stem Cell Foundation. Only a graduate student in 2007, he has quickly established himself as a leader in the epigenetics field.

"It just happens to be that we're at the right time and at the right place, both physically and sort of in time, " Meissner says. "Just five years ago, we would have had the same question, but we wouldn't have had the same tools to answer the question."

Summary
DNA methylation is a defining feature of mammalian cellular identity and is essential for normal development1, 2. Most cell types, except germ cells and pre-implantation embryos3, 4, 5, display relatively stable DNA methylation patterns, with 70–80% of all CpGs being methylated6. Despite recent advances, we still have a limited understanding of when, where and how many CpGs participate in genomic regulation. Here we report the in-depth analysis of 42 whole-genome bisulphite sequencing data sets across 30 diverse human cell and tissue types. We observe dynamic regulation for only 21.8% of autosomal CpGs within a normal developmental context, most of which are distal to transcription start sites. These dynamic CpGs co-localize with gene regulatory elements, particularly enhancers and transcription-factor-binding sites, which allow identification of key lineage-specific regulators. In addition, differentially methylated regions (DMRs) often contain single nucleotide polymorphisms associated with cell-type-related diseases as determined by genome-wide association studies. The results also highlight the general inefficiency of whole-genome bisulphite sequencing, as 70–80% of the sequencing reads across these data sets provided little or no relevant information about CpG methylation. To demonstrate further the utility of our DMR set, we use it to classify unknown samples and identify representative signature regions that recapitulate major DNA methylation dynamics. In summary, although in theory every CpG can change its methylation state, our results suggest that only a fraction does so as part of coordinated regulatory programs. Therefore, our selected DMRs can serve as a starting point to guide new, more effective reduced representation approaches to capture the most informative fraction of CpGs, as well as further pinpoint putative regulatory elements.

The research was funded by the National Institutes of Health and the New York Stem Cell Foundation..

Original press release:http://www.eurekalert.org/pub_releases/2013-08/hu-hre080813.php