title: Myc-induced anchorage of the rDNA IGS region to nucleolar matrix modulates growth-stimulated changes in higher-order rDNA architecture.
abstract: Chromatin domain organization and the compartmentalized distribution of chromosomal regions are essential for packaging of deoxyribonucleic acid (DNA) in the eukaryotic nucleus as well as regulated gene expression. Nucleoli are the most prominent morphological structures of cell nuclei and nucleolar organization is coupled to cell growth. It has been shown that nuclear scaffold/matrix attachment regions often define the base of looped chromosomal domains in vivo and that they are thereby critical for correct chromosome architecture and gene expression. Here, we show regulated organization of mammalian ribosomal ribonucleic acid genes into distinct chromatin loops by tethering to nucleolar matrix via the non-transcribed inter-genic spacer region of the ribosomal DNA (rDNA). The rDNA gene loop structures are induced specifically upon growth stimulation and are dependent on the activity of the c-Myc protein. Matrix-attached rDNA genes are hypomethylated at the promoter and are thus available for transcriptional activation. rDNA genes silenced by methylation are not recruited to the matrix. c-Myc, which has been shown to induce rDNA transcription directly, is physically associated with rDNA gene looping structures and the intergenic spacer sequence in growing cells. Such a role of Myc proteins in gene activation has not been reported previously.
authors.affiliation: Clinical Research Center (KFC), Department of Laboratory Medicine and Center for Biosciences, Karolinska Institute, SE-141 86 Huddinge, Sweden.
authors.forename: Chiou-Nan
authors.initials: CN
authors.lastname: Shiue
authors.affiliation: Clinical Research Center (KFC), Department of Laboratory Medicine and Center for Biosciences, Karolinska Institute, SE-141 86 Huddinge, Sweden.
authors.forename: Amir
authors.initials: A
authors.lastname: Nematollahi-Mahani
authors.affiliation: Clinical Research Center (KFC), Department of Laboratory Medicine and Center for Biosciences, Karolinska Institute, SE-141 86 Huddinge, Sweden anthony.wright@ki.se.
authors.forename: Anthony P H
authors.initials: AP
authors.lastname: Wright
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D021903:DNA, Ribosomal Spacer / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D051381:Rats
chemical_list: D021903:DNA, Ribosomal Spacer; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc