TFs for TEs: the transcription factor repertoire of mammalian transposable elements

Abstract

Transposable elements (TEs) are genetic elements capable of changing position within the genome. Although their mobilization can constitute a threat to genome integrity, nearly half of modern mammalian genomes are composed of remnants of TE insertions. The first critical step for a successful transposition cycle is the generation of a full-length transcript. TEs have evolved cis-regulatory elements enabling them to recruit host-encoded factors driving their own, selfish transcription. TEs are generally transcriptionally silenced in somatic cells, and the mechanisms underlying their repression have been extensively studied. However, during germline formation, preimplantation development, and tumorigenesis, specific TE families are highly expressed. Understanding the molecular players at stake in these contexts is of utmost importance to establish the mechanisms regulating TEs, as well as the importance of their transcription to the biology of the host. Here, we review the transcription factors known to be involved in the sequence-specific recognition and transcriptional activation of specific TE families or subfamilies. We discuss the diversity of TE regulatory elements within mammalian genomes and highlight the importance of TE mobilization in the dispersal of transcription factor-binding sites over the course of evolution.

Keywords: co-option; regulatory elements; retrotransposons; transcriptional regulation.

Figure 1.

Schematic representation of the regulatory elements of major human and mouse TEs. Boxes represent the different parts of the elements, as indicated. For L1s, the light-blue box represents the YY1-binding site. For the SINE elements, A and B refer to the A and B boxes. (ERVs) Endogenous retroviruses, (LTR) long terminal repeat, (UTR) untranslated region, (ORF) open reading frame, (ASP) antisense promoter.

Figure 2.

Preimplantation development is a window of opportunity for vertical transmission. All cells during preimplantation development will contribute to the germline; hence, a new insertion occurring during preimplantation development has increased chances to be transmitted to the next generation by vertical transmission. A new insertion will also be present in cells of the ExE and Epi, which is represented as a red star in the schematic representation of these tissues. (TE) Transposable element, (ICM) inner cell mass, (ExE) extraembryonic endoderm, (Epi) epiblast, (PGCs) primordial germ cells. Mouse drawing was adapted from https://www.clker.com/clipart-simple-black-and-whitemouse.html.