Epigenetic regulatory role of MORC2 in human brain development
(2025) MOBN03 20242Degree Projects in Molecular Biology
- Popular Abstract
- Close encounters of the TE kind: molecular consequences of MORC2 mutations
Nearly half of our DNA is composed of transposable elements (TEs), sequences that can copy and move around within the genome. When they move, they can disrupt the stability of our genome and cause damage to our cells.
In response to that, cells have evolved mechanisms to minimize their movements. One protein that represses TE activity is MORC2. It packs the DNA tightly which makes it harder for TEs to move. There are mutations in MORC2 that have been associated with several brain disorders.
In this project, we explored how two disease-associated MORC2 mutations change the activity of transposable elements in human cells. We found that these mutations... (More) - Close encounters of the TE kind: molecular consequences of MORC2 mutations
Nearly half of our DNA is composed of transposable elements (TEs), sequences that can copy and move around within the genome. When they move, they can disrupt the stability of our genome and cause damage to our cells.
In response to that, cells have evolved mechanisms to minimize their movements. One protein that represses TE activity is MORC2. It packs the DNA tightly which makes it harder for TEs to move. There are mutations in MORC2 that have been associated with several brain disorders.
In this project, we explored how two disease-associated MORC2 mutations change the activity of transposable elements in human cells. We found that these mutations activate a specific type of transposable elements called LINE-1 (L1) and excessively silence KRAB-ZNFs, which are proteins that themselves help control transposable elements. This imbalance in L1 activity disrupts the survival of cells that give rise to neurons which make up our brains. Blocking the L1 activity improved the survival of those cells, potentially linking the L1 activation to brain development. Additionally, we found that the excessive repression of KRAB-ZNFs can lead to broader changes in DNA packaging which can potentially affect many locations in the genome.
Overall, these findings show that MORC2 has a complex role in controlling transposable elements and the proteins that keep them in check. This project sheds light on potential consequences of TE activity and provides new insights into the complexes and mechanisms that control their activity in the context of human health.
Master’s degree project in Molecular Biology, 60 credits, 2025
Department of Biology, Lund University
Advisor: Dr. Christopher Douse, Laboratory of Epigenetics and Chromatin Dynamics
Department of Experimental Medical Science, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9214696
- author
- Matijević, Jana
- supervisor
- organization
- course
- MOBN03 20242
- year
- 2025
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9214696
- date added to LUP
- 2025-10-30 14:24:01
- date last changed
- 2025-10-30 14:24:01
@misc{9214696,
author = {{Matijević, Jana}},
language = {{eng}},
note = {{Student Paper}},
title = {{Epigenetic regulatory role of MORC2 in human brain development}},
year = {{2025}},
}