Active RB causes visible changes in nuclear organization.
Active RB causes visible changes in nuclear organization.
复制标题
活性RB引起核组织的明显变化。
DOI：
10.1083/jcb.202102144
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发表时间：
2022-03-07
期刊：
影响因子：
--
通讯作者：
Dyson NJ
中科院分区：
文献类型：
--
作者：
Krishnan B;Yasuhara T;Rumde P;Stanzione M;Lu C;Lee H;Lawrence MS;Zou L;Nieman LT;Sanidas I;Dyson NJ
Krishnan等人使用FISH表明，特定形式的RB诱导了常染色质和异染色质结构域组织的变化。这些变化在显微镜下可见，发生在细胞周期停止后，与衰老分开，并且代表了不依赖于e2f的RB活性。RB通过抑制E2F来限制G1/S进展。本研究表明，持续表达活性RB和延长G1阻滞会导致染色体结构的明显变化，而这些变化与E2F抑制没有直接关系。使用FISH探针对两个常染色质RB相关区域，两个缺乏RB结合位点的异染色质结构域和两个全染色体探针，我们发现组成型活性RB （ΔCDK-RB）促进了更分散、分散和分散的染色质组织。这些变化是RB依赖的，是由单磷酸化RB的特定同工型驱动的，并且需要已知的RB相关活性。ΔCDK-RB改变了rb结合的基因组位点之间的物理相互作用，但rb诱导的染色体结构变化不受显性阴性DP1的影响。rb诱导的变化似乎是广泛的，并影响染色体在细胞核内的定位。基因表达谱显示，分散表型与增加的自噬反应有关。我们推断，在细胞周期阻滞后，RB通过非规范机制显著改变核组织，这种重组与细胞状态的转变有关。
Krishnan et al. use FISH to show that specific forms of RB induce changes in the organization of euchromatin and heterochromatin domains. These changes are visible under the microscope, occur after cell cycle arrest, are separable from senescence, and represent an E2F-independent activity of RB. 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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影响因子：
5.3
作者：
He, S;Cook, BL;Weintraub, SJ
通讯作者：
Weintraub, SJ
影响因子：
13.6
作者：
Criscione SW;De Cecco M;Siranosian B;Zhang Y;Kreiling JA;Sedivy JM;Neretti N
通讯作者：
Neretti N
影响因子：
8.8
作者：
Chandra T;Ewels PA;Schoenfelder S;Furlan-Magaril M;Wingett SW;Kirschner K;Thuret JY;Andrews S;Fraser P;Reik W
通讯作者：
Reik W
影响因子：
--
作者：
Beliveau, Brian J;Apostolopoulos, Nicholas;Wu, Chao-ting
通讯作者：
Wu, Chao-ting
DOI：
10.1038/s41568-018-0008-5
发表时间：
2018-07
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Dick FA;Goodrich DW;Sage J;Dyson NJ
通讯作者：
Dyson NJ