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Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
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Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
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Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
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Journal Article
Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
2015
Overview
Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Hox genes are targets of Polycomb proteins and form local 3D clusters centered on the H3K27me3 mark. More distal contacts have also been described, yet their selectivity, dynamics, and relation to other layers of chromatin organization remained elusive. We report that repressed Hox genes form mutual intra- and interchromosomal interactions with other genes located in strong domains labeled by H3K27me3. These interactions occur in a central and active nuclear environment that consists of the HiC compartment A, away from peripheral lamina-associated domains. Interactions are independent of nearby H3K27me3-marked loci and determined by chromosomal distance and cell-type–specific scaling factors, thus inducing a moderate reorganization during embryogenesis. These results provide a simplified view of nuclear organization whereby Polycomb proteins may have evolved to repress genes located in gene-dense regions whose position is restricted to central, active, nuclear environments.
Significance The development of an embryo from a single fertilized cell is orchestrated by a large set of key regulatory genes whose activities need to be precisely controlled. Proteins from the Polycomb group (PcG) family maintain the inactive state of these genes by modifying the surrounding histone H3 tails. Here we report that these inactive genes contact other PcG-rich regions within otherwise active environments in the cell nucleus, suggesting the presence of repressive microenvironments. PcG positive genes interact independently from neighboring genes, depending on their linear distance and more global chromosome folding characteristics, with only moderate changes during embryonic development.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Cells
/ Chromosomes, Mammalian - genetics
/ Chromosomes, Mammalian - metabolism
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryo, Mammalian - metabolism
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - metabolism
/ Female
/ Gene Expression Regulation, Developmental
/ histones
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Male
/ Mammals
/ Mice
/ Nuclear Proteins - metabolism
/ Oligonucleotide Array Sequence Analysis
/ Polycomb-Group Proteins - genetics
/ Polycomb-Group Proteins - metabolism
/ Proteins
