Jumping Genes regulate Neurons

[shunyadragon]

Virus-Like “Jumping” DNA Regulates Human Neurons
TOPICS:EPFLGeneticsNeuroscience

By EPFL AUGUST 28, 2020

The human genome contains over 4.5 million sequences of DNA called “transposable elements,” these virus-like entities that “jump” around and help regulate gene expression. They do this by binding transcription factors, which are proteins that regulate the rate of transcription of DNA to RNA, influencing gene expression in a broad range of biological events.

Now, an international team of scientists led by Didier Trono at EPFL has discovered that transposable elements play a significant role in influencing the development of the human brain. The study is published in Science Advances.

The scientists found that transposable elements regulate the brain’s development by partnering up with two specialized proteins from the family of proteins known as “Krüppel-associated box-containing zinc finger proteins, or KZFPs. In 2019, another study led by Trono showed that KZFPs tamed the regulatory activity of transposable elements in the first few days of the fetus’s life. However, they suspected that these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

The researchers identified two KZFPs as specific only to primates, and found that they are expressed in specific regions of the human developing and adult brain. They further observed that these proteins kept controlling the activity of transposable elements — at least in neurons and brain organoids cultured in the lab. As a result, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

“These results reveal how two proteins that appeared only recently in evolution have contributed to shape the human brain by facilitating the co-option of transposable elements, these virus-like entities that have been remodeling our ancestral genome since the dawn of times,” says Didier Trono. “Our findings also suggest possible pathogenic mechanisms for diseases such as amyotrophic lateral sclerosis or other neurodegenerative or neurodevelopmental disorders, providing leads for the prevention or treatment of these problems.”

Reference: “Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons” by Priscilla Turelli, Christopher Playfoot, Dephine Grun, Charlène Raclot, Julien Pontis, Alexandre Coudray, Christian Thorball, Julien Duc, Eugenia V. Pankevich, Bart Deplancke, Volker Busskamp and Didier Trono, 28 August 2020, Science Advances.
DOI: 10.1126/sciadv.aba3200."

 

[icehorse]

Great gif, interesting article, thanks.

Our startup is always looking at advances in cognitive sciences and trying to figure out ways to apply these findings. For example, as researchers are learning about proteins like CREB-2, we can connect a few dots and conclude (with some degree of certainty), that when teaching material (in the form of books or lectures or videos), is dry, abstract, and boring, the brain's natural design is to inhibit the creation of long term memories.

I wonder if anyone is thinking about practical applications for the work you cited above?

The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB | Molecular Brain | Full Text

 

[Cooky]

Virus-Like “Jumping” DNA Regulates Human Neurons
TOPICS:EPFLGeneticsNeuroscience

By EPFL AUGUST 28, 2020

The human genome contains over 4.5 million sequences of DNA called “transposable elements,” these virus-like entities that “jump” around and help regulate gene expression. They do this by binding transcription factors, which are proteins that regulate the rate of transcription of DNA to RNA, influencing gene expression in a broad range of biological events.

Now, an international team of scientists led by Didier Trono at EPFL has discovered that transposable elements play a significant role in influencing the development of the human brain. The study is published in Science Advances.

The scientists found that transposable elements regulate the brain’s development by partnering up with two specialized proteins from the family of proteins known as “Krüppel-associated box-containing zinc finger proteins, or KZFPs. In 2019, another study led by Trono showed that KZFPs tamed the regulatory activity of transposable elements in the first few days of the fetus’s life. However, they suspected that these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

The researchers identified two KZFPs as specific only to primates, and found that they are expressed in specific regions of the human developing and adult brain. They further observed that these proteins kept controlling the activity of transposable elements — at least in neurons and brain organoids cultured in the lab. As a result, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

“These results reveal how two proteins that appeared only recently in evolution have contributed to shape the human brain by facilitating the co-option of transposable elements, these virus-like entities that have been remodeling our ancestral genome since the dawn of times,” says Didier Trono. “Our findings also suggest possible pathogenic mechanisms for diseases such as amyotrophic lateral sclerosis or other neurodegenerative or neurodevelopmental disorders, providing leads for the prevention or treatment of these problems.”

Reference: “Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons” by Priscilla Turelli, Christopher Playfoot, Dephine Grun, Charlène Raclot, Julien Pontis, Alexandre Coudray, Christian Thorball, Julien Duc, Eugenia V. Pankevich, Bart Deplancke, Volker Busskamp and Didier Trono, 28 August 2020, Science Advances.
DOI: 10.1126/sciadv.aba3200."

"these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left"

...And the fact that they're only found in humans.

...This is very complex and perplexing.

 

[shunyadragon]

"these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left"

...And the fact that they're only found in humans.

...This is very complex and perplexing.

Careful, this at present is a new discovery found in humans, and it cannot be concluded that they are 'only' in humans.

 

[Cooky]

Careful, this at present is a new discovery found in humans, and it cannot be concluded that they are 'only' in humans.

I guess the fact that the article states: "These results reveal how two proteins that appeared only recently in evolution" is throwing me off...

And also: "The researchers identified two KZFPs as specific only to primates"

...It also says these transposable elements have been: "remodeling our ancestral genome since the dawn of times"

So it's a little confusing for me to understand.

 

[shunyadragon]

I guess the fact that the article states: "These results reveal how two proteins that appeared only recently in evolution" is throwing me off...

And also: "The researchers identified two KZFPs as specific only to primates"

...It also says these transposable elements have been: "remodeling our ancestral genome since the dawn of times"

So it's a little confusing for me to understand.

This does not mean this type of 'Jumping Genes' does not occur in other species.

 

[Cooky]

This does not mean this type of 'Jumping Genes' does not occur in other species.

Ok, I get it now... Only the particular proteins exist in primates, which the transposable elements are able to effect.

But these transposable elements could be found to exist elsewhere, minus the ability to influence neurons due to the lack of special proteins, found exclusively in primate DNA.

...Because "Krüppel-associated box-containing zinc finger proteins" are only found in primates... Exclusively.

 

[shunyadragon]

Ok, I get it now... Only the particular proteins exist in primates, which the transposable elements are able to effect.

But these transposable elements could be found to exist elsewhere, minus the ability to influence neurons due to the lack of special proteins, found exclusively in primate DNA.

...Because "Krüppel-associated box-containing zinc finger proteins" are only found in primates... Exclusively.

Not due to the lack, but alternate proteins with a similar function.

 

[Aupmanyav]

Everything is possible. Good research. Carry on, Boys.

 

[Heyo]

Virus-Like “Jumping” DNA Regulates Human Neurons
TOPICS:EPFLGeneticsNeuroscience

By EPFL AUGUST 28, 2020

The human genome contains over 4.5 million sequences of DNA called “transposable elements,” these virus-like entities that “jump” around and help regulate gene expression. They do this by binding transcription factors, which are proteins that regulate the rate of transcription of DNA to RNA, influencing gene expression in a broad range of biological events.

Now, an international team of scientists led by Didier Trono at EPFL has discovered that transposable elements play a significant role in influencing the development of the human brain. The study is published in Science Advances.

The scientists found that transposable elements regulate the brain’s development by partnering up with two specialized proteins from the family of proteins known as “Krüppel-associated box-containing zinc finger proteins, or KZFPs. In 2019, another study led by Trono showed that KZFPs tamed the regulatory activity of transposable elements in the first few days of the fetus’s life. However, they suspected that these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

The researchers identified two KZFPs as specific only to primates, and found that they are expressed in specific regions of the human developing and adult brain. They further observed that these proteins kept controlling the activity of transposable elements — at least in neurons and brain organoids cultured in the lab. As a result, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

“These results reveal how two proteins that appeared only recently in evolution have contributed to shape the human brain by facilitating the co-option of transposable elements, these virus-like entities that have been remodeling our ancestral genome since the dawn of times,” says Didier Trono. “Our findings also suggest possible pathogenic mechanisms for diseases such as amyotrophic lateral sclerosis or other neurodegenerative or neurodevelopmental disorders, providing leads for the prevention or treatment of these problems.”

Reference: “Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons” by Priscilla Turelli, Christopher Playfoot, Dephine Grun, Charlène Raclot, Julien Pontis, Alexandre Coudray, Christian Thorball, Julien Duc, Eugenia V. Pankevich, Bart Deplancke, Volker Busskamp and Didier Trono, 28 August 2020, Science Advances.
DOI: 10.1126/sciadv.aba3200."

Interesting article but calling transposable elements "jumping" or "virus-like" is more confusing than helping. They have little in common with viruses and "Jumping Genes" already has a meaning in genetics.

 

[sun rise]

The more we find out about how life works, the more I am in awe of its beautiful complexity.