Epigenetic and transcriptional effects of full-length LINE-1 retrotransposons in human neural progenitor cells
(2021) BINP52 20202Degree Projects in Bioinformatics
- Abstract
- Transposable elements (TE) are parasitic genetic entities that have the ability to alter their position within a genome and have the potential to influence its functionality. Although TEs play beneficial roles in the evolution of their host, they are active in various human disorders including neurological diseases, where may contribute to the progress of the disease. Long Interspersed Nuclear Element-1(LINE-1, L1) is the dominant, autonomously-transposing TE family in all mammals and some the evolutionary-young LINE-1s are thought to be active in human neural progenitor cells (NPCs). We defined the epigenetic environment and transcriptional activity of the seven evolutionary-youngest L1 subfamilies in human NPCs, and compared this profile... (More)
- Transposable elements (TE) are parasitic genetic entities that have the ability to alter their position within a genome and have the potential to influence its functionality. Although TEs play beneficial roles in the evolution of their host, they are active in various human disorders including neurological diseases, where may contribute to the progress of the disease. Long Interspersed Nuclear Element-1(LINE-1, L1) is the dominant, autonomously-transposing TE family in all mammals and some the evolutionary-young LINE-1s are thought to be active in human neural progenitor cells (NPCs). We defined the epigenetic environment and transcriptional activity of the seven evolutionary-youngest L1 subfamilies in human NPCs, and compared this profile to human endogenous retroviruses (HERVs). Our analysis of two heterochromatin associated histone methylation marks (H3K9me3, H3K27me3) suggested that H3K9me3 is responsible for silencing a majority of the studied TEs, whereas H3K27me3 is significantly less present. Profiling of two epigenetic marks associated with transcriptional activity (H3K4me1, H3K4me3) revealed that the presence of H3K4me3 is a better predicter of LINE-1 transcription than H3K4me1 for those elements that evade repression. Furthermore, we investigated the transcriptional differences between human and chimpanzee NPCs, focusing in particular on genes containing human-specific LINE-1 elements (L1HS). We found 11 genes containing a full-length L1HS sequence that showed downregulation in human compared to the chimpanzee NPCs. A Chi-square test suggested dependency between the presence of L1HS and thedownregulation of genes, perhaps due to induction of H3K9me3-heterchromatin. Looking ahead, this project provides a base for further exploration of functional roles of LINE-1 elements in human NPCs and a template to investigate mechanisms of LINE-1 and HERV regulation by chromatin regulators (Less)
- Popular Abstract
- Defining activity of L1 elements in human neural progenitors
Transposable elements (TEs) are mobile genetic components that can change their position in our DNA and some of them can do so independently. Because of their mobility, they can have both positive and negative functional effects on our DNA. Changes in activity of these elements has also been reported in various neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. We explore the activity of these elements in early human brain development cells and investigate some of their effects.
With the increasing lifespan of humans over the years, there is also an increase in the number of cases of neurodegenerative disorders. One of the most effective ways of finding... (More) - Defining activity of L1 elements in human neural progenitors
Transposable elements (TEs) are mobile genetic components that can change their position in our DNA and some of them can do so independently. Because of their mobility, they can have both positive and negative functional effects on our DNA. Changes in activity of these elements has also been reported in various neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. We explore the activity of these elements in early human brain development cells and investigate some of their effects.
With the increasing lifespan of humans over the years, there is also an increase in the number of cases of neurodegenerative disorders. One of the most effective ways of finding a treatment for these diseases is by studying the functional aspects of human neural development. Allowing us to do so are advancements which enables scientists to create a neural progenitor cells (NPC) from patients. These cells can further develop into majority of neurons and glia of the human cerebral cortex, which confirms their importance in studying neurodevelopment. Using this method, we derived NPCs from two human samples which were used to analyze the activity of TEs.
TEs comprise about half of our DNA and besides inherent mobility they can also functionally affect neural development. Additionally, they have also been shown directly to contribute to the onset of neurological disorders. Thus, understanding TEs is essential as we can compare diseased and healthy samples which can further speed up the development of treatments for these disorders. Using specific epigenetic marks correlated to either repression or activity, we investigated a family of transposable elements named L1, which isthe dominant, independent TE in human DNA. Interestingly, besides additional functional effects, this family contains one member found exclusively in humans named L1HS.
Although we found overwhelming repression of L1 elements, some members of the seven youngest L1s, including L1HS, showed potential for activity in human NPCs. We also observed that more than half of the L1s competent for functional regulation are located around genes, which the L1s can be further activate or repress. Finally, we compared the activity of human genes found near the human specific L1HS, to the activity of the parallel genes found in chimpanzees. This is possible because humans and chimpanzees show great similarity between the DNA sequence. The comparison of activity showed that repression of specific genes occurred specifically due to the presence of L1HS elements, with a probability of only 0.05% that it occurs by chance. This can be further used not only in treatment of disorders, but in understanding how our brain develops and why is it so different from other mammals.
Master’s degree project in Bioinformatics, 60 ECTS, 2021
Department of Biology, Lund University
Advisor: Christopher Douse
Advisors unit: Molecular Neurogenetic Laboratory (Johan Jakobsson (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9059342
- author
- Pandiloski, Ninoslav
- supervisor
- organization
- course
- BINP52 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9059342
- date added to LUP
- 2021-06-28 12:11:35
- date last changed
- 2021-06-28 12:11:35
@misc{9059342,
abstract = {{Transposable elements (TE) are parasitic genetic entities that have the ability to alter their position within a genome and have the potential to influence its functionality. Although TEs play beneficial roles in the evolution of their host, they are active in various human disorders including neurological diseases, where may contribute to the progress of the disease. Long Interspersed Nuclear Element-1(LINE-1, L1) is the dominant, autonomously-transposing TE family in all mammals and some the evolutionary-young LINE-1s are thought to be active in human neural progenitor cells (NPCs). We defined the epigenetic environment and transcriptional activity of the seven evolutionary-youngest L1 subfamilies in human NPCs, and compared this profile to human endogenous retroviruses (HERVs). Our analysis of two heterochromatin associated histone methylation marks (H3K9me3, H3K27me3) suggested that H3K9me3 is responsible for silencing a majority of the studied TEs, whereas H3K27me3 is significantly less present. Profiling of two epigenetic marks associated with transcriptional activity (H3K4me1, H3K4me3) revealed that the presence of H3K4me3 is a better predicter of LINE-1 transcription than H3K4me1 for those elements that evade repression. Furthermore, we investigated the transcriptional differences between human and chimpanzee NPCs, focusing in particular on genes containing human-specific LINE-1 elements (L1HS). We found 11 genes containing a full-length L1HS sequence that showed downregulation in human compared to the chimpanzee NPCs. A Chi-square test suggested dependency between the presence of L1HS and thedownregulation of genes, perhaps due to induction of H3K9me3-heterchromatin. Looking ahead, this project provides a base for further exploration of functional roles of LINE-1 elements in human NPCs and a template to investigate mechanisms of LINE-1 and HERV regulation by chromatin regulators}},
author = {{Pandiloski, Ninoslav}},
language = {{eng}},
note = {{Student Paper}},
title = {{Epigenetic and transcriptional effects of full-length LINE-1 retrotransposons in human neural progenitor cells}},
year = {{2021}},
}