The Epigenetic Control of Transposable Elements in Development and in Diseases

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About this Research Topic

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Background

Eukaryotic genomes are historical records of successive Transposable Elements (TEs) invasions. Transposable elements and their remnants constitute nearly 50% of the human genome and their tight regulation is essential for normal development. TEs have historically been considered as “selfish” genetic elements that threaten genomic stability through their capability to move around the genome. Consistently, their aberrant activity has been linked to sterility and cancer. However, during specific stages of early development TEs are not only transcribed, but their expression is essential for normal development. In addition TEs can also act as driver of genomic evolution and influence neighbouring gene expression. An important question in biology is how transposable elements are regulated.

While chromatin accessibility is known to significantly influence TE activity, the mechanistic aspects of this regulation have not been established and a series of questions remain unanswered. What is the hierarchy of events that lead to TE silencing? What are the chromatin factors necessary for TE regulation? Is this regulation inherited trans-generationally? Multiple epigenetic mechanisms may serve as a biological memory that maintains specific regulatory marks at loci harboring TEs, thus affecting cellular function. A thorough understanding of these mechanisms is especially important, considering that aberrant expression of TEs can lead to developmental defects and is associated with many diseases, including cancer, neurodegenerative disorders and haemophilia. In cancer cells, repressive chromatin modifications are often lost from TEs and it has been proposed that TE reactivation can lead to new mutations and genomic instability. However, recent evidence suggest that TE reactivation can also induce an immune response responsible for killing cancer cells. A better understanding of the contradictory roles of TEs, and the mechanisms by which the aberrant activity of chromatin factors can result in TE dysregulation is essential for a thorough understanding of many physiological and pathological processes.

In this Research topic, we aim to cover recent developments in the field of Transposable Elements regulation and we encourage authors to submit original research, reviews, resources, opinions and perspectives including, but not limited to, any one or more of the following themes:

• Epigenetic mechanisms of trans generational inheritance relative to the regulation of TEs
• Chromatin-dependent mechanisms of TE regulation
• Implication of TE dysregulation in diseases/ Effect of TE activity on genomic instability/ Interplay between TEs and immune signaling
• The role of TE regulation in development
• Advances in integrative and bioinformatic analysis of repetitive elements

Keywords: Transcription, Genome Integrity, Epigenetic, hromatin, Transposable Elements

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