'Jumping' DNA regulates human neurons

Date:
August 28, 2020
Source:
Ecole Polytechnique Fe'de'rale de Lausanne
Summary:
'Jumping' sequences of DNA, known as transposable elements,
partner up with evolutionarily recent proteins to influence the
differentiation and physiological functioning of human neurons.



FULL STORY ==========================================================================
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 "Kru"ppel-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."

========================================================================== Story Source: Materials provided by
Ecole_Polytechnique_Fe'de'rale_de_Lausanne. Original written by Nik Papageorgiou. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Priscilla Turelli, Christopher Playfoot, Dephine Grun, Charle`ne
Raclot,
Julien Pontis, Alexandre Coudray, Christian Thorball, Julien Duc,
Eugenia V. Pankevich, Bart Deplancke, Volker Busskamp, Didier
Trono. Primate- restricted KRAB zinc finger proteins and target
retrotransposons control gene expression in human neurons. Science
Advances, 2020; 6 (35): eaba3200 DOI: 10.1126/sciadv.aba3200 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200828140310.htm

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