title: Organization of transcriptional regulatory machinery in osteoclast nuclei: compartmentalization of Runx1.
abstract: The osteoclast is a highly polarized multinucleated cell that resorbs bone. Using high resolution immunofluorescence microscopy, we demonstrated that all nuclei of an osteoclast are transcriptionally active. Each nucleus within the osteoclast contains punctately organized microenvironments where regulatory complexes that support transcriptional and post-transcriptional control reside. Functional equivalency of osteoclast nuclei is reflected by similar representation of regulatory proteins that support ribosomal RNA synthesis (nucleolin), mRNA transcription (RNA polymerase II, bromouridine triphosphate), processing of gene transcripts (SC35), signal transduction (NF-kappaB), and phenotypic gene expression (Runx1). Our results establish that gene regulatory machinery is architecturally associated and compartmentalized within intranuclear microenvironments of the multiple nuclei of osteoclasts to support physiologically responsive modifications in cellular structural and functional properties.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01655, USA.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Saltman
authors.forename: Amjad
authors.initials: A
authors.lastname: Javed
authors.forename: John
authors.initials: J
authors.lastname: Ribadeneyra
authors.forename: Sadiq
authors.initials: S
authors.lastname: Hussain
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Young
authors.forename: Philip
authors.initials: P
authors.lastname: Osdoby
authors.forename: Alla
authors.initials: A
authors.lastname: Amcheslavsky
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Zvi
authors.initials: Z
authors.lastname: Bar-Shavit
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015530:Nuclear Matrix / Q000378:metabolism; D009928:Organ Specificity; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C493726:Runx1 protein, mouse; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors