Abstract
Epigenetic changes of gene expression can potentially be reversed by developmental programs, genetic manipulation, or pharmacological interference. However, a case of transcriptional gene silencing, originally observed in tetraploid Arabidopsis thaliana plants, created an epiallele resistant to many mutations or inhibitor treatments that activate many other suppressed genes. This raised the question about the molecular basis of this extreme stability. A combination of forward and reverse genetics and drug application provides evidence for an epigenetic double lock that is only alleviated upon the simultaneous removal of both DNA methylation and histone methylation. Therefore, the cooperation of multiple chromatin modifications can generate unanticipated stability of epigenetic states and contributes to heritable diversity of gene expression patterns.
Highlights
Determined loss of gene expression by mutation, insertion of transposons, or chromosomal rearrangements is usually irreversible, since the chance of precisely reconstituting the original DNA sequence is low
Seeds from the diploid line C2S1 with the inactive HPT and seeds from the HPT-expressing, hygromycin-resistant line C2R were germinated and plantlets grown for 3 weeks on plates containing 10 mg/mL of hygromycin in combination with 40 mM ZEB and/or 1.6 mM trichostatin A (TSA), concentrations that were previously described to be effective in reactivating silenced targets and reducing methylation in all possible sequence contexts (Baubec et al, 2009) or were even higher than effective concentrations (Chang and Pikaard, 2005)
An undisputed definition of epigenetic inheritance is still lacking, but most descriptions refer to its reversible nature to distinguish it from genetic alterations inscribed in the DNA sequence
Summary
Determined loss of gene expression by mutation, insertion of transposons, or chromosomal rearrangements is usually irreversible, since the chance of precisely reconstituting the original DNA sequence is low. Epigenetic loss of gene activity is defined as not affecting the DNA sequence but rather as chemically modifying DNA and associated proteins, altering the packaging of chromatin and its accessibility for the transcription machinery. Affected sequences are kept transcriptionally inactive by well-characterized pathways that establish DNA methylation and/or histone modifications. For several of these modifications, antagonistic enzymes have been described (Chen and Tian, 2007; Pfluger and Wagner, 2007; Ooi and Bestor, 2008), and many epigenetically regulated sequences undergo a cycle of silencing and activation in the life cycle of the organism.
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