Organization of transcriptional regulatory machinery in osteoclast nuclei: compartmentalization of Runx1.
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.
Saltman
Laura H
LH
Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01655, USA.
Javed
Amjad
A
Ribadeneyra
John
J
Hussain
Sadiq
S
Young
Daniel W
DW
Osdoby
Philip
P
Amcheslavsky
Alla
A
van Wijnen
Andre J
AJ
Stein
Janet L
JL
Stein
Gary S
GS
Lian
Jane B
JB
Bar-Shavit
Zvi
Z
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
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