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Review
. 2022 Aug 11;11(16):2501.
doi: 10.3390/cells11162501.

All Quiet on the TE Front? The Role of Chromatin in Transposable Element Silencing

Luisa Di Stefano  1
Affiliations
Review

All Quiet on the TE Front? The Role of Chromatin in Transposable Element Silencing

Luisa Di Stefano. Cells. .

Abstract

Transposable elements (TEs) are mobile genetic elements that constitute a sizeable portion of many eukaryotic genomes. Through their mobility, they represent a major source of genetic variation, and their activation can cause genetic instability and has been linked to aging, cancer and neurodegenerative diseases. Accordingly, tight regulation of TE transcription is necessary for normal development. Chromatin is at the heart of TE regulation; however, we still lack a comprehensive understanding of the precise role of chromatin marks in TE silencing and how chromatin marks are established and maintained at TE loci. In this review, I discuss evidence documenting the contribution of chromatin-associated proteins and histone marks in TE regulation across different species with an emphasis on Drosophila and mammalian systems.

Keywords: chromatin; transcriptional regulation; transposable elements.

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Conflict of interest statement

I declare no conflict of interest.

Figures

Figure 1
Figure 1
Impact of TEs on their host genome. (A) Examples of how TEs can impact genomes. (B) Schematic representation of a how insertion of a transposable element (TE) into the open reading frame of the coagulation factor VIII (F8) gene can induce insertional mutagenesis. This mutation was found in patients with hemophilia [1]. (C) Schematic representation of TE-induced ectopic recombination. (D) An example of TE domestication. Ancient env genes from ERVs have evolved into syncytin genes, which are involved in placenta formation [8]. Another example not represented here is that of Rag1 and Rag2, which are involved in V(D)J somatic recombination in the immune system of vertebrates [18]. (E) An example of a TE transcript (LINE1) acting as an RNA scaffold for chromatin regulators and transcription factors. (F) TE sequences carry transcription factor binding sites, and their insertion can lead to novel gene-regulatory patterns in the host organism. (G) Example of how a TE can modulate chromatin by inducing the spread of heterochromatin. Abbreviations: E, exon; TE, transposable element; LTR, long terminal repeat; ORF, open reading frame; UTR, untranslated region; CR, chromatin regulator; TF, transcription factor.
Figure 1
Figure 1
Impact of TEs on their host genome. (A) Examples of how TEs can impact genomes. (B) Schematic representation of a how insertion of a transposable element (TE) into the open reading frame of the coagulation factor VIII (F8) gene can induce insertional mutagenesis. This mutation was found in patients with hemophilia [1]. (C) Schematic representation of TE-induced ectopic recombination. (D) An example of TE domestication. Ancient env genes from ERVs have evolved into syncytin genes, which are involved in placenta formation [8]. Another example not represented here is that of Rag1 and Rag2, which are involved in V(D)J somatic recombination in the immune system of vertebrates [18]. (E) An example of a TE transcript (LINE1) acting as an RNA scaffold for chromatin regulators and transcription factors. (F) TE sequences carry transcription factor binding sites, and their insertion can lead to novel gene-regulatory patterns in the host organism. (G) Example of how a TE can modulate chromatin by inducing the spread of heterochromatin. Abbreviations: E, exon; TE, transposable element; LTR, long terminal repeat; ORF, open reading frame; UTR, untranslated region; CR, chromatin regulator; TF, transcription factor.
Figure 2
Figure 2
Schematic representation of the mobilization mechanisms of transposable elements. (A) Schematic representation of the “copy-and-paste” mobilization mechanism of retrotransposons. Retrotransposons replicate through an RNA intermediate and a reverse transcription step. LTR retrotransposons produce a double-stranded DNA (dsDNA) intermediate that integrates into a new locus, whereas non-LTR retrotransposons retrotranscribe directly at the target locus after cleaving genomic DNA, a process known as ‘target-primed reverse transcription’. (B) Schematic representation of the “cut-and-paste” and “peel-and-paste” mobilization mechanisms of DNA transposons. Both mobilization mechanisms require the excision of the transposon DNA from its original locus and its reintegration into another locus, but the “peel-and-paste” mechanism requires the formation of a circular double-stranded DNA (dsDNA) intermediate. The mechanism of replication of maverick and crypton elements has not been determined. (C,D) Classification of eukaryotic transposable elements (as proposed by Wicker et al. [21,22]). Genetic structures of representative transposable elements from each order. Yellow boxes represent open reading frames (ORFs), and grey boxes represent non-coding domains. Element lengths are not to scale. Abbreviations: LTR, long terminal repeat; ORF, open reading frame; UTR, untranslated region; ENV, envelope protein; GAG, capsid protein; RT, reverse transcriptase; RH, ribonuclease H domain; ITR, inverted terminal repeat; TR, terminal repeat; EN, endonuclease; YR, tyrosine recombinase; TIR, terminal inverted repeats; Tase, transposase; REP, replication initiator; Hel, helicase; C-INT, integrase; ATP, packaging ATPase; CYP, cysteine protease; POL B, DNA polymerase B.
Figure 3
Figure 3
Modulation of chromatin organization and gene transcription by histone lysine methylation. A schematic representation of euchromatin and heterochromatin showing the main lysine methyl marks on histone H3 and their prevalent localization in the genome (euchromatin and heterochromatin). Abbreviations: K, lysine; TSS, transcriptional start site; M, methyl residue.
Figure 4
Figure 4
Models of chromatin-mediated transposon-silencing mechanisms. (A) Schematic representation of the factors implicated in TE silencing in Drosophila (B) and in mammals. Multiple mechanisms exist to repress TEs both in flies and in mice, including piRNA-directed silencing mediated by the Piwi/MIWI2-piRNAs complex, DNA methylation-dependent silencing mediated by DNMTs (in mammals), KDM1a-dependent histone demethylation and KRAB-ZNF-KAP1-mediated silencing. Whether these layers of control of TE silencing collaborate on the same TEs or act on different TEs or in different cell types/tissues remains to be fully elucidated.
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Grants and funding

L.D.S. research is supported by the French National Research Agency (ANR-20-CE12-0015-01), the CNRS and the INSERM.

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