Abstract
Epigenetic regulation of gene expression, including by Polycomb Group (PcG) proteins, may depend on heritable chromatin states, but how these states can be propagated through mitosis is unclear. Using immunofluorescence and biochemical fractionation, we find PcG proteins associated with mitotic chromosomes in Drosophila S2 cells. Genome-wide sequencing of chromatin immunoprecipitations (ChIP–SEQ) from mitotic cells indicates that Posterior Sex Combs (PSC) is not present at well-characterized PcG targets including Hox genes in mitosis, but does remain at a subset of interphase sites. Many of these persistent sites overlap with chromatin domain borders described by Sexton et al. (2012), which are genomic regions characterized by low levels of long range contacts. Persistent PSC binding sites flank both Hox gene clusters. We hypothesize that disruption of long-range chromatin contacts in mitosis contributes to PcG protein release from most sites, while persistent binding at sites with minimal long-range contacts may nucleate re-establishment of PcG binding and chromosome organization after mitosis.
Highlights
Epigenetic mechanisms, including those used by the essential Polycomb Group (PcG) proteins, mediate stable inheritance of gene expression patterns through mitotic divisions
We find that PcG proteins remain associated with mitotic chromatin, and a small subset of PcG binding sites throughout the genome is maintained between interphase and mitosis
These persistent binding sites preferentially overlap borders of chromatin domains. These results suggest a model in which PcG proteins retained at border sites may nucleate re-binding of PcG protein within domains after mitosis
Summary
Epigenetic mechanisms, including those used by the essential PcG proteins, mediate stable inheritance of gene expression patterns through mitotic divisions. Binding of many transcription factors and chromatin regulators is disrupted in mitosis through posttranslational modification of the proteins or their chromatin substrate [1,2,3]. PcG proteins are required to maintain gene silencing during development and in differentiated cells (reviewed in [10,11,12,13,14,15]) These proteins assemble into multiprotein complexes with an array of enzymatic and structural effects on chromatin (for detailed reviews on the biochemistry of PcG proteins, see [16,17]). The status of long range interactions in mitosis is not known
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