Project #1: The impact of domesticated TE-derived sequences

 

The impact of TE-derived sequences on human pluripotency

Dr. Jichang Wang

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).

 

The role of CP2 family in pluripotency

PhD student Chuanbo Sun

The maintenance of hPSC pluripotency is involved in the regulatory networks of a serials transcription factors. OCT4, SOX2 and NANOG are the widely known core transcription factors that act cooperatively to form the regulatory network of pluripotency. Recently, TFCP2l1 (LBP9) has been recognized as a potential transcription factor that in conjunction with HERVH is involved in human pluripotent network. LBP9 belongs to CP2 family, which the family members share great similarity in amino acid sequence. We are working on how CP2 family is involved in the self-renewal and differentiation potential in human pluripotent cells.

 

Cross-talk of ERVs and host factors in re-wiring transcriptional networks in primates

PhD student Manvendra Singh

Transcriptional expression of repetitive elements originating from endogenous retroviruses (ERVs) in human cell-types is tightly controlled by host factors. Despite systematically expressed, they are differentially expressed during different stages of early embryogenesis. Host genome and transcriptome has been modified by multiple waves of retroviral insertions. We investigate the cross-talk between host-factors and ERVs during primate evolution (collaboration with L. D. Hurst, University of Bath, UK) and in various human cell lines. Analysis of our data and recently published datasets enables us to look into the complexity of regulatory networks and the possible involvement of spatio-temporal expression and repression of retroelements in biological processes.

 

 

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

Dr. Tamás Raskó and Dr. Attila Szvetnik

A high throughput yeast two hybrid screen identified cellular interactors of Sleeping Beauty and piggyBac transposases. This finding has important ramification for the presence of domesticated piggyBac-like elements in the human genome.

 

Deciphering the function of an evolutionary conserved medium reiterated frequency repeat (MER)

PhD student Vaishnavi Raghunathan

TEs make the most significant components of both prokaryotic and eukaryotic genomes, and have been widely regarded as molecular parasites owing to their potential to give rise to a variety of genetic alterations. These alterations might interrupt gene function. Alternatively, TEs could make themselves useful to the host genome (domestication). Due to their mobile nature, TEs have likely played a key role in distributing non-coding, regulatory elements in the vertebrate genome. Medium reiterated frequency repeats-6 (MER6), are a class of DNA transposons belonging to Tc1-Mariner-Tigger family of interspersed repeats. We propose to identify the potential impact of the evolutionary conserved MER6.