Chromatin contributes to structural integrity of promyelocytic leukemia bodies through a SUMO-1-independent mechanism.
Promyelocytic leukemia (PML) protein is implicated in transcriptional regulation, apoptosis, DNA repair, and tumor suppression. It is not known, however, whether PML and other components of PML bodies function within the vicinity of the bodies or elsewhere in the nucleoplasm. In this study, we demonstrate that chromatin organization around PML bodies influences their morphology, dynamics, and structural integrity by a SUMO-1-independent mechanism. Following transcriptional inhibition and during early apoptosis, chromatin retracts from the periphery of PML bodies, coinciding with the formation of new PML-containing structures through fission of supramolecular PML-containing microbodies. Both fission and fusion of microbodies with parental PML bodies indicate a loss of structural integrity of the bodies, dependent on the state of the surrounding chromatin. This is supported by the observation that treatment of live cells with DNase I could reproduce the structural instability of PML bodies. In addition, PML bodies, which are normally surrounded by chromatin and are positionally stable, become more dynamic following these treatments, presumably due to the loss of chromatin contacts. Overexpression of SUMO-1, a modification required for PML body formation, did not prevent PML body fission, indicating that chromatin-based integrity of PML body structure occurs through a SUMO-1-independent mechanism.
Eskiw
Christopher H
CH
Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Dellaire
Graham
G
Bazett-Jones
David P
DP
D017209:Apoptosis; D002460:Cell Line; D002843:Chromatin / Q000502:physiology* / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D002843:Chromatin; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D003609:Dactinomycin