title: H3K9 acetylation and radial chromatin positioning.
abstract: Histone variants and their epigenetic modifications determine genome function, particularly transcription. However, whether regulation of gene expression can be influenced by nuclear organization or vice versa is not completely clear. Here, we analyzed the effect of epigenetic changes induced by a histone deacetylase inhibitor (HDACi) on the nuclear radial rearrangement of select genomic regions and chromosomes. The HDACi, sodium butyrate (NaBt), induced differentiation of human adenocarcinoma HT29 cells as well as a genome-wide increase in H3K9 acetylation. Three-dimensional analysis of nuclear radial distributions revealed that this increase in H3K9 acetylation was often associated with a repositioning of select loci and chromosomes toward the nuclear center. On the other hand, many centromeres resided sites more toward the nuclear periphery, similar to sites occupied by chromosome X. In more than two-thirds of events analyzed, central nuclear positioning correlated with a high level of H3K9 acetylation, while more peripheral positioning within interphase nuclei correlated with a lower level of acetylation. This was observed for the gene-rich chromosomes 17 and 19, TP53, and CCND1 genes as well as for gene-poor chromosome 18, APC gene, regions of low transcriptional activity (anti-RIDGEs), and the relatively transcriptionally less active chromosome X. These results are consistent with a role for epigenetic histone modifications in governing the nuclear radial positioning of genomic regions during differentiation.
authors.affiliation: Department of Molecular Cytology and Cytometry, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Ludek
authors.initials: L
authors.lastname: Strasák
authors.forename: Eva
authors.initials: E
authors.lastname: Bártová
authors.forename: Andrea
authors.initials: A
authors.lastname: Harnicarová
authors.forename: Gabriela
authors.initials: G
authors.lastname: Galiová
authors.forename: Jana
authors.initials: J
authors.lastname: Krejcí
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D002877:Chromosomes, Human / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17 / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000378:metabolism; D002888:Chromosomes, Human, Pair 19 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D020895:Enterocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D002087:Butyrates; C530104:CCND1 protein, human; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D006655:Histone Deacetylases