Abstract
BackgroundEpigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; however, their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing.ResultsUsing an attP system in Drosophila, we find that the so-called neutral chromatin environments vary substantially in their ability to support the silencing activity of the well-characterized bxdPRE. In refractory chromosomal contexts, factors required for PcG-silencing are unable to gain access to the PRE. Silencing activity can be rescued by linking the bxdPRE to a boundary element (insulator). When placed next to the PRE, the boundaries induce an alteration in chromatin structure enabling factors critical for PcG silencing to gain access to the bxdPRE. When placed at a distance from the bxdPRE, boundaries induce PSS by bringing the bxdPREs on each homolog in close proximity.ConclusionThis proof-of-concept study demonstrates that the repressing activity of PREs can be induced or enhanced by nearby boundary elements.Graphical abstract
Highlights
Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms
Results bxdPRE silencing activity depends on the chromosomal context In previous studies, polycomb response elements (PREs) were found to repress expression of reporter genes in only about half of the transgene insertion sites [38,39,40,41, 58, 59]
The silencing activity of the bxdPRE was assessed by the reduction in eye pigmentation as pigmentation is known to be directly correlated with the level of white gene transcription [62, 63]
Summary
Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing. PcG and TrxG proteins control the transcriptional activity of the Hox complex genes, and many other genes implicated in different aspects of development and differentiation. Disruption of the PcG or TrxG maintenance systems can result in developmental abnormalities and other pathologies [11,12,13,14,15,16]
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