A ripple effect: skipping a single exon in PTBP1 leads to changes in splicing and neural differentiation

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What makes a human, human? Or a chicken, chicken?

The preeminent belief has been that the difference between species lies in their DNA—the number of genes an organism has, the function of those genes and when and where those genes are expressed. As it turns out, the answer is not quite so simple.

“There’s very high conservation of the total number of protein coding genes across different vertebrate species,” says Serge Gueroussov, a PhD student in Dr. Benjamin Blencowe’s lab at the University of Toronto. “When [researchers] compared gene expression across different organs in different species, there was also a lot of conservation. It suggests that organisms don’t differ so much in the genes they have and the extent to which they express [those genes].”

In other words, while we may look drastically different from a frog or a chicken, our repertoire of genes and when and where we express those genes are actually pretty similar. So where is the variation coming from?

The answer may lie, in part, in a process called alternative splicing. Continue reading

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[Guest post] Tit for tet: Tet3 regulates neuron activity through epigenetic changes

Please welcome Eat, Read, Science’s first guest blogger Julia Turan! Today she’ll be sharing a cool new paper looking at how changes in our DNA change the way our neurons talk to one another.

Sequence the human genome. Check. Now all that’s left is to understand how the letters of our DNA alphabet are accessed in the context of different types of cells and microscopic environments. Completing the sequence was no small feat but we have plenty of work ahead. This field is known as epigenetics: the study of factors—inside or outside our body limits—that turn genes on or off and influences how our cells read the genome.

Nature and nurture. Two words frequently tossed around in biology. Epigenetics takes these formerly opposing concepts and swirls them together. Our nature is being nurtured. Our experiences are altering the expression of our DNA. Really let that sink in.

A term coined by C.H. Waddington (known as ‘Wad’ to his friends) in 1942, epigenetics was first studied in embryonic development. As we morph from wad to body (pun intended), cells with the same DNA blueprint become part of team lung, blood, brain, etc. Epigenetic mechanisms control this differentiation of cells. There are two important traits of these changes: 1) the DNA sequence is not directly altered, rather its expression—how it is read out and turned into a protein—is; and 2) these changes can persist after the cell divides and even in the organism’s progeny.

Thanks to Hongjun Song and his team at Johns Hopkins University, we now know that experience also influences genetic expression in the incredible three-pound clump beneath our skulls. Their research showed that these changes don’t just happen during stress, aging or neurodegenerative diseases. They are happening in all of our brains at this very moment. The chemical structure of the DNA in your brain is actively regulated in response to what you’re experiencing. These processes are essential to the stability of our brain circuits and potentially its disruption during disease. Continue reading