Active RB causes visible changes in nuclear organization
Name
jcb_202102144.pdf
Description
Published version
Size
8.3 MB
Format
Adobe PDF
Checksum (MD5)
bb150d7e22293a3f7c8c4d7c0391a46d
Author(s)
Krishnan, Badri
Yasuhara, Takaaki
Rumde, Purva
Stanzione, Marcello
Lu, Chenyue
Lee, Hanjun
Lawrence, Michael S
Zou, Lee
Nieman, Linda T
Sanidas, Ioannis
Date Issued
March 7, 2022
Journal
Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Badri Krishnan, Takaaki Yasuhara, Purva Rumde, Marcello Stanzione, Chenyue Lu, Hanjun Lee, Michael S. Lawrence, Lee Zou, Linda T. Nieman, Ioannis Sanidas, Nicholas J. Dyson; Active RB causes visible changes in nuclear organization. J Cell Biol 7 March 2022; 221 (3): e202102144.
Version
Final published version
Abstract
RB restricts G1/S progression by inhibiting E2F. Here, we show that sustained expression of active RB, and prolonged G1 arrest, causes visible changes in chromosome architecture that are not directly associated with E2F inhibition. Using FISH probes against two euchromatin RB-associated regions, two heterochromatin domains that lack RB-bound loci, and two whole-chromosome probes, we found that constitutively active RB (ΔCDK-RB) promoted a more diffuse, dispersed, and scattered chromatin organization. These changes were RB dependent, were driven by specific isoforms of monophosphorylated RB, and required known RB-associated activities. ΔCDK-RB altered physical interactions between RB-bound genomic loci, but the RB-induced changes in chromosome architecture were unaffected by dominant-negative DP1. The RB-induced changes appeared to be widespread and influenced chromosome localization within nuclei. Gene expression profiles revealed that the dispersion phenotype was associated with an increased autophagy response. We infer that, after cell cycle arrest, RB acts through noncanonical mechanisms to significantly change nuclear organization, and this reorganization correlates with transitions in cellular state.
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DOI of Published Version
https://doi.org/10.1083/jcb.202102144
