Izsvák Lab

The impact of TE-derived sequences on human pluripotency

Dr. Jichang Wang*, Alexandra Konraskhina, Karam Ibrahim

Most of TEs and TE-derived sequences are transcriptionally inactive in somatic cells. However, due to the DNA de-methylation, some families of TEs can be transcriptionally reactivated during early development. Recent studies show that a family of retrotransposon, ERVL is uniquely reactivated in 2-cell embryo stage in mice, and might be associated with the totipotency. These studies indicate that some families of retroelements, such as HERVH might have roles in the acquisition and maintenance of pluripotency. Using the human pluripotent stem cells as models, our main interest is to decipher the potential biological functions of TEs in human pluripotency (press release).

Deciphering the function of domesticated TE-derived sequences in the human genome

Tamás Raskó and Attila Szvetnik*, Kathrin Radscheit, Amit Pande

Domesticated functions of the PiggyBac (PB) Transposable Element Derived genes (PGBD1-5)

One of the most exciting challenges in evolutionary studies is to find out how a new gene was born. We find it particularly challenging to understand where a new gene comes from, how does a novel function evolve, and how/why does the host organisms allow a new gene to survive? Although transposable elements (TEs) are considered as selfish creatures, inactivated TEs are frequently used as building boxes to generate novel cellular functions for the benefit of the host-organism.

The human genome comprises five PiggyBac (PB) Transposable Element Derived genes (PGBD1-5). Although some members of the PGBD family have been associated with diseases, the domesticated function(s) of these genes are unknown.

To understand the evolutionary process of domestication, and whether specific properties of the PB transposase were preferentially adapted, we are characterizing the members of the PGBD family in humans. Based on structural predictions and evolutionary conservation, we systematically characterize which protein functions are inherited from the ancient transposase, and aim at deciphering what their domesticated function could be.

While the function of PGBD3 and PGBD5 are partially characterized, only little is known about the other three PGBD genes. Here, we try to decipher the biological role of the human domesticated PGBD1, PGBD4 transposase-derived genes, which are the derivatives of the piggyBac transposase.

PGBD1 has been identified in two independent GWAS studies, as a susceptibility locus for schizophrenia. Our studies indicate that PGBD1 is associated with cellular processes including, protein folding, stress response, oxidative stress, cell survival and differentiation. Remarkably, PGDB1 is a key regulator of (lnc)NEAT1 expression in neural progenitors. Dysfunctional PGBD1 is implicated in certain neural diseases, including SCA1 and schizophrenia. doi.org/10.1101/2021.05.19.444448

We also try to uncover the molecular function of PGBD4. Based on our preliminary results PGBD4 seems to be involved in the regulation of RNA splicing.