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Posts Tagged epigenetics

Is a genome enough? (Not Just DNA #1) Grant Jacobs Oct 02

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Answering a question from the Tuatara genome blog and starting a new series, Not Just DNA.[1]

We are entering the age of the genome.[2]

Our genomes tell us about ourselves. Genome sequences show our evolutionary relationships with other species. They reveal the origin and migration of humans. Unwelcome changes to our genomes can bring disability or illness; understanding genetic variation may bring personalised medicine. We can peer at the genetics of a yet-to-be-born child. DNA sequences are evidence for courtrooms and can track the source of an infectious disease outbreak.

But do we need to know more than the DNA sequence of a genome to understand it? It may be a question with a self-evident answer, but it’s important with so much effort being put into genome sequencing.

Genomes are being sequenced from just about everywhere you can imagine. Source: genomesonline.org Genome map.

Genomes are being sequenced from just about everywhere you can imagine. Source: genomesonline.org Genome map.

Plans are well advanced to sequence over a hundred thousand human genomes and the genomes of thousands of different species.[3] Genomics England are set to sequence the genomes of 100,000 Brits over the next five years. (The 1000 genomes project was started in 2008 and published last year.) Personal genome sequencing is to found internationally. Genomes of individuals include an Australian aborigine, from various tribes in Africathe southern tip of India and different Asian groups among many others including the Neanderthal genome. In New Zealand, we have a pilot project for the use of genomics in medical diagnosis. Organised efforts are working through a long list of species whose genomes are being sequenced: the Genome 10K project aims to sequence 10,000 vertebrates, roughly one for every vertebrate genus; the i5K initiative is to do the same for 5,000 insects and arthropods.

There are many more projects like this – and this is just the beginning. It’s much more that the human genome sequence and a few things that happened afterwards.

Knowing our genome

Our genomes are central to who we are and are often described as a blueprint for us.

Book-of-genome-640px

A book of human genome sequence text at Tokyo University museum. (Credit: Ben Casey; Source: Wikimedia, CC 3.0) This is just one book, the full genome is much bigger. The Wellcome Collection has the human genome in just over 100 similar books.

A better description would be that our genomes code for a collection of parts that our biology can choose from to use to build us.

book-genome-436px

Until a genome sequence is marked up with what each bit of DNA does, it makes for pretty tedious reading. Edited from Ben Casey, CC 3.0; Source: Wikimedia.

As our bodies grow, it’s the choice of what parts to use, when, and the interaction of those parts that make us.

Those interactions include interacting with the genome itself.

How do these bits used together to make us?

Does the DNA sequence by itself code for all of this?

Not just for our genomes, but also the genomes of the thousands of different species being sequenced.

A question asked a few weeks ago on the Tuatara Genome project blog was if the chemical modifications of the DNA were also needed to be known to make sense of a genome[4]:

“What about epigenetic markers? How important are these when considering if all the genomic information has been captured?”

The wider question is what makes a genome ‘work’?

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Terry Speed on Epigenetics Grant Jacobs Jun 21

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Epigenetics is an increasingly used jazz word, and I don’t just mean by scientists. You can see it in magazine articles, marketing spiels, and so on.*

It’s touted as some kind of new, special genetics.

Epigenetics itself isn’t new. It’s basically the business of how our cells express their genetics, how the characteristics of a particular cell type (or organ or animal) are realised from it’s genes.

Some things we’re learning about epigenetics are new, however.

But you don’t have to hear these from me.** You can listen to Terry Speed’s public lecture on epigenetics, given during a particularly strong winter storm in New Zealand’s capital city, Wellington. (Given that, we ought to praise those who attended too.)

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Epigenetic dynamics – free Grant Jacobs Mar 15

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Those with interests in epigenetics and genome structure may want to check out Nature Structural and Molecular Biology’s focus on epigenetic dynamics. (This gives me an opportunity to briefly sound off on a favourite topic…)

One fascinating development over the past few years has been explorations of the three-dimensional nature of genomes, how they are arranged within the nucleus of our cells, how the spatial organisation of genomes might affect how genes are used, interactions between parts of our genomes and far, far too many other questions…

I guess you could say you know an interesting area of science by the questions it raises.

Yeast genome model. From Duan et al, Nature, 2010.

Yeast genome model. From Duan et al, Nature, 2010.

As a student, I studied proteins that bind DNA and the protein-DNA interactions they make. I’m still interested in that—old interests don’t die that easily in science—but these things now fall within a wide range of aspects.

Although a relatively short list of reviews, the focus on epigenetic dynamics covers an interesting range of topics that illustrate how studying gene regulation have moved from simple beginnings of the immediate promoter and protein binding sites in DNA of the 1980s (or so) to the rich complexity of DNA and histone modifications, nucleosome (re-)positioning, protein complexes, chromatin loops, chromosomal domains, regulatory RNAs and more.*

Particularly appealing is that all of the articles are free for anyone to read.**

(Original from Luger lab, sourced from Biomedical Beat.)

(Original from Luger lab, sourced from Biomedical Beat.)

Speaking for myself, it’s great to see a more ‘spatial’ thinking about genomes emerge in molecular biology over the past few years. One of the appealing things about 3-D genome structure work (to me) is that it shifts whole genomes into computational structural biology rather than the more ‘linear’ approach typical of the current genome projects.***

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Epigenetics – introductory explanations Grant Jacobs Feb 06

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Epigenetics is a term that is increasingly being heard of outside of molecular biology or genetics.

One of my interests is how gene regulation works, how the molecules that control genes do their thing. You can think of epigenetics as gene regulation through controlling the availability of genes to be used or not.

While it’s fairly easy to offer some examples of epigenetics, it’s harder to present it a balanced way, in part because understanding it needs a little context, a little explanation of how it fits into the rest of the what‘s going on in the nucleus—the place the DNA is stored in our cells—while our bodies develop and grow.

This TED lecture by Dr. Courtney Griffin from the Cardiovascular Biology Research Program at the Oklahoma Medical Research Foundation gives some of the background.

YouTube Preview Image

It’s a little drier than many TED lectures*—but a lot lighter than formal lectures on the topic!—and worth viewing if you’d like to know more about epigenetics.

A lighter presentation is this from NOVA ScienceNow by Neil Tyson. Lest you think he’s not a star, Neil Tyson has over a million twitter followers.** (And counting.)

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Structured procrastination, 2 Dec 2012 Grant Jacobs Dec 03

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Another edition of my irregular structured procrastination reading lists – have fun exploring these. (Geekier ones nearer the end.)

Sci-fi movie

Geneticist Ricki Lewis offers a review of Jim, which she says is more compelling than GATTACA. The movie can be viewed on-line. (If you watch it, let me know what you think.)

Gene-based dating

You think gene-based dating in sci-fi? It’s already with us. See also this twitter conversation. (There’s also a service that matches dates by their dogs.)

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Structured procrastination, 23-Aug-2012 edition Grant Jacobs Aug 23

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Long-time readers will know ‘Structured procrastinations’ are when I point to interesting or quirky articles, usually on the less academic side, to clear tabs out of my web browser.

What was that about impact factors, Nature? Criticising their inflated status under a banner headlining your own impact factor…

(Original seen on twitter, by Petro Baltrao; reproduced with permission.)

If impact factors interest you, read Stephen Curry’s article Sick of Impact Factors, which has lots of excellent commentary following it. Fellow sciblogger, Siouxsie has a short take on Stephen’s article, Statistically illiterate…

There’s a new history of science blog over at the Guardian, The H Word. There’s three H’s there – history, Higgitt and Heggie, the authors. They aim to cover the history of science, institutions, instruments and museums.

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Epigenetics overview (video) Grant Jacobs Apr 11

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Below Jessica Tyler, from the University of Texas MD Anderson Cancer Center, introduces epigenetics, a topic I’ve touched on a few times and would like to elaborate further on. Her introduction is fairly gentle; hopefully some of the essence of the thing will come across to non-specialists!

You may need to wait until the video is buffered before it starts displaying. Feel free to ask questions in the comments below.

(Excuse the back-to-back videos and no articles – I’m very busy until at least Friday!)

Other articles on Code for life:

Epigenetics, growing old and identical twins becoming unique

Doggie ERVs

Transcribing a gene, free poster

Autism — looking for parent-of-origin effects

Coiling bacterial DNA

Epigenetics and 3-D gene structure

Transcribing a gene, free poster Grant Jacobs Jan 30

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If you’re looking for a pictorial overview of gene transcription–the process of making a RNA copy of a gene–or just like making up posters to put on your walls, you might like to download this free poster (1.94 Mb PDF) from Nature Reviews Genetics by Vikki Weake and Jerry Workman.

transcription-cycle-poster-all-640px

As you can see it’s very large, so I can’t show you more than a small portion in a scale that you can read.

Although intended for scientists, if you are familiar with the basics of transcription this might give some idea of what scientists now think goes on. (There will–of course–be more to add!)

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Find transcription factor motifs in genomes better: add histone acetylation data Grant Jacobs Oct 14

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A ‘lite’ review of an attempt to improve motif screening of genomes using additional data. Considering local minima of histone acetylation in a context of high histone acetylation may be one way forward.

A number of years ago at a biotechnology sector after-talk drinks I found myself trying to convince a CEO that often the better way to improve a predictive method is not to continually refine the one measure, which often results in a ’law of diminishing returns’ effect, but to find a complementary independent measure and use the original measure and the new measure together to improve the prediction success.

Recent years have seen similar approaches taken to improve scanning genomes for transcription factor binding sites.

Transcription factors regulate the rate of expression of genes by binding short DNA sequences in the genome, in neighbour of the gene they regulate.

Conceptually at least, the epigenetic state of a region of the genome controls if the gene is accessible to be used and hence be the target of a transcription factor.*

(Original from Luger lab, sourced from Biomedical Beat.)

Array of nucleosomes. The ‘tails’ that are chemically modified are indicated with dashed lines. (Original from Luger lab, sourced from Biomedical Beat.)

DNA in eukaryotes is packaged using histone proteins into arrays of nucleosomes. Chemical modification of the histone proteins correlate with the nature of the packing of the DNA, to form either condensed or open chromatin. Active genes are associated with open chromatin.

Open chromatin – portions of the genome associated with genes that are actively being used –are charactered by a number of features in their chromatin such as the acetylation of histone H4.

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Friday fare Grant Jacobs Oct 08

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Time for the weekly round-up of lighter fare.

Ancient Greece is a (Grecian) myth The Onion puts out the odd gem, such as this report of an announcement that historians have entirely fabricated ancient Greece. Here’s an excerpt to get you started:

The group acknowledged that the idea of a sophisticated, flourishing society existing in Greece more than two millennia ago was a complete fiction created by a team of some two dozen historians, anthropologists, and classicists who worked nonstop between 1971 and 1974 to forge “Greek” documents and artifacts.

“Honestly, we never meant for things to go this far,” said Professor Gene Haddlebury, who has offered to resign his position as chair of Hellenic Studies at Georgetown University. “We were young and trying to advance our careers, so we just started making things up: Homer, Aristotle, Socrates, Hippocrates, the lever and fulcrum, rhetoric, ethics, all the different kinds of columns–everything.”

The Onion is a great place for light relief. Other headlines include: ’10 Million Killed Annually By Stepping Out Of Comfort Zones’ (here) and ’Teen With Cancer Vows It Won’t Keep Her From Being Mean, Moody Little Shit’ (great title, but the article doesn’t quite live up to it in my opinion).

(H/T @BoraZ)

Map of the on-line community xkcd has an enormous map of the on-line community, click on the image for the full cartoon/sketch.

Updated map of online communities (Source: xkcd.)

Updated map of online communities (Source: xkcd.)

Travel prize for ScienceOnline2011 Those hoping to get to the ScienceOnline2011 (un)conference (that includes yours truly) might be interested in this competition. The two best evolution blog posts chosen by two judges and the online science community will receive $US750 towards attending the meeting. The competition is not limited to those in the USA. Applications close December 1st.

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