Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes.
The nuclear localization of genes is intimately tied to their transcriptional status in Saccharomyces cerevisiae, with populations of both active and silent genes interacting with components of the nuclear envelope. We investigated the relationship between the mammalian nuclear pore and the human genome by generating high-resolution, chromosome-wide binding maps of human nucleoporin 93 (Nup93) in the presence and absence of a potent histone deacetylase inhibitor (HDACI). Here, we report extensive genomic reorganization with respect to the nuclear pore following HDACI treatment, including the recruitment of promoter regions, euchromatin-rich domains, and differentially expressed genes. In addition to biochemical mapping, we visually demonstrate the physical relocalization of several genomic loci with respect to the nuclear periphery. Our studies show that inhibiting HDACs leads to significant changes in genomic organization, recruiting regions of transcriptional regulation to mammalian nuclear pore complexes.
Brown
Christopher R
CR
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Kennedy
Caleb J
CJ
Delmar
Valerie A
VA
Forbes
Douglass J
DJ
Silver
Pamela A
PA
D000107:Acetylation; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002885:Chromosomes, Human, Pair 16 / Q000378:metabolism; D002895:Chromosomes, Human, Pair 5 / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000032:analysis / Q000378:metabolism*
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D028861:Nuclear Pore Complex Proteins; C508154:Nup93 protein, human; C012589:trichostatin A