Transposable elements (TEs) are ubiquitous in prokaryotic and eukaryotic genomes and are believed to have greatly impacted genome evolution. Effects of TEs within genomes include insertional mutagenesis, chromosomal breakage, genome
rearrangement and illegitimate recombination (see reviews 71-73). A benefit of TEs acting as “controlling elements” facilitating the evolution of adaptive regulatory effects has been
proposed 73. Such effects could include influencing the transcript levels of adjacent genes (positively or negatively), by acting as enhancers or promoters, producing alternative splice variants, or altering polyadenylation patterns following transposition into new sites. Hence, despite their mutagenic potential, the adaptive flexibility conferred to the host genome might explain the persistence of these elements throughout evolution 72.
With the advent of genome-wide sequencing over the past decade, it is now clear TEs comprise a significant fraction of most eukaryote genomes. Two major classes of mobile elements exist: DNA transposons and retrotransposons. Autonomous DNA
transposons have terminal inverted repeats (TIRs) and a single open reading frame (ORF) that encodes a transposase. If the element’s coding capacity has been lost, but the cis-sequences necessary for transposition remain, it is considered non-autonomous. Indeed, the first elements characterized, the “Dissociation-Activator two-unit” system, included a non-autonomous element (Ds) that could only transpose or break chromosomes when the transposase of another autonomous locus (Ac) was present 74. A key feature of DNA transposons is that transposition starts by nicking the transposon and target site ends, followed by a stand transfer reaction catalyzed by the transposase 75. Replicative transposition occurs if this intermediate complex is replicated, leaving the donor site unaltered, while a new copy of the transposon in gained at the acceptor site 75. Nonreplicative transposition occurs when the transposon physically moves (“cut and paste”) to the acceptor site leaving a potentially lethal, double stand DNA break at the donor site 75. As briefly stated above, only two transposons families, CACTA (CAC1 and CAC2) and AtMu1, have been reported to become mobile in hypomethylated Arabidopsis mutants 16-18. Notably, no activity has been reported in met1 single mutants.
The above transposition mechanisms separate DNA transposons from elements that require their encoded transcript (mRNA) as the transposition intermediate, known as retrotransposons. Eukaryotic genomes have three types of retrotransposons that can be divided based on structure: LTR retrotransposons with long terminal repeats (LTRs) in direct orientation that encode reverse transcriptase (RT) and/or integrase (e.g. Ty1 and Copia); non-LTRs retroelements without terminal repeats that encode RT and/or endonuclease (e.g. LINEs); and a nonviral superfamily without terminal repeats and without coding capacity (e.g. SINEs). The retrotransposon lifecycle generally includes transcription, translation, reverse transcription and subsequent integration of element cDNA into the acceptor site (“copy and paste”) 75.
Paradoxically, transcription does not necessarily correlate with transposition. For example, in yeast, an average of only one Ty1 cDNA is integrated into the genome for every 14,000 Ty1 transcripts 76. Thus, despite their high copy number in plant genomes, very few active retrotransposons have been identified in plants (see refs 77,78). More importantly, no report exists for active, endogenous retroelements in A. thaliana.
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CHAPTER TWO: TRANSGENERATIONAL EPIGENETIC INHERITANCE OF DNA METHYLATION IN THE met1-3 EPIGENOME