Heterochromatin is enriched for specific epigenetic factors including Heterochromatin Protein 1a (HP1a), and is essential for many organismal functions. To elucidate heterochromatin organization and regulation, we purified Drosophila melanogaster HP1a interactors, and performed a genome-wide RNAi screen to identify genes that impact HP1a levels or localization. The majority of the over four hundred putative HP1a interactors and regulators identified were previously unknown. We found that 13 of 16 tested candidates (83%) are required for gene silencing, providing a substantial increase in the number of identified components that impact heterochromatin properties. Surprisingly, image analysis revealed that although some HP1a interactors and regulators are broadly distributed within the heterochromatin domain, most localize to discrete subdomains that display dynamic localization patterns during the cell cycle. We conclude that heterochromatin composition and architecture is more spatially complex and dynamic than previously suggested, and propose that a network of subdomains regulates diverse heterochromatin functions.
Epigenetics and chromatin factors
Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.” PLoS Genet, 8, 4, Pp. e1002646.Abstract
. 2012. “
Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.” PLoS Genet, 8, 7, Pp. e1002830.Abstract
. 2012. “
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.” PLoS One, 11, 4, Pp. e0153970.Abstract
. 2016. “
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia.” PLoS Genet, 6, 6, Pp. e1000994.Abstract
. 2010. “
Identification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen.” PLoS Genet, 8, 5, Pp. e1002667.Abstract
. 2012. “
Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20.” Mol Cell, 48, 1, Pp. 28-38.Abstract
. 2012. “
A genome-wide RNA interference screen identifies putative chromatin regulators essential for E2F repression.” Proc Natl Acad Sci U S A, 104, 22, Pp. 9381-6.Abstract
. 2007. “
A functional insulator screen identifies NURF and dREAM components to be required for enhancer-blocking.” PLoS One, 9, 9, Pp. e107765.Abstract
. 2014. “
Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation.” J Cell Biol, 183, 5, Pp. 805-18.Abstract
. 2008. “