Jumping DNA plays a significant role in regulating human neurons

Jumping DNA regulates human neurons.

Transposable elements (TEs), also known as “jumping genes,” are DNA sequences that move from one location on the genome to another. The fact that roughly half of the human genome is made up of TEs.

These transposable elements help regulate gene expression 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, a study by EPFL has discovered a more role of TEs. The transposable elements play a significant role in influencing the development of the human brain.

They do this by teaming up with two specialized proteins from the family of proteins known as “Krüppel-associated box-containing zinc finger proteins, or KZFPs.

Last year, a study found that KZFPs regulate tamed the regulatory activity of transposable elements in the first few days of the fetus’s life. However, these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

Scientists identified two KZFPs as explicit to primates and found that they are expressed in explicit areas of the human developing and adult brain. They further observed that these proteins kept controlling transposable elements’ activity– at any rate in neurons and brain organoids cultured in the lab.

Therefore, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as protecting these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

Didier Trono at EPFL said, “These results reveal how two proteins that appeared only recently in evolution have contributed to shaping 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. 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:
  1. Priscilla Turelli et al. Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Science Advances 6:eaba3200, 28 August 2020. DOI: 10.1126/sciadv.aba3200

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