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RNA-seq and ChIP-seq analysis of BMI1 or RING1B-silenced prostate cancer cells C4-2

ABSTRACT: Purpose: Study of the role of BMI1 dependent and indpendent of PRC1 in castration-resistant prostate cancer(CRPC) Method: The expression of BMI1 or RING1B was silenced by 2 independent siRNA strands targeted at BMI1 or RING1B in C4-2 cells, scramble RNA as control. mRNA profiles and genome-wide chromatin-state maps were generated by deep sequencing. AR, BMI1 and IgG ChIP was conducted in C4-2 cells. Results: AR-induced genes were significantly down regulated by BMI1 knockdown but not RING1B. higher expression levels of BMI1 activated genes (those downregulated by BMI1 knockdown) were significantly associated with poorer disease-free and poorer overall survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97831 | GEO | 2018/02/07

REPOSITORIES: GEO

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Project description:NguyenLK2011 - Ubiquitination dynamics in Ring1B-Bmi1 system This theoretical model investigates the dynamics of Ring1B/Bmi1 ubiquitination to identify bistable switch-like and oscillatory behaviour in the system. Michaelis-Menten (MM) equations are used to formulate the model. However, the authors show that the dynamics persist even for Mass-Action kinetics. This SBML file is the MM version of the model. This model is described in the article: Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. Nguyen LK, Muñoz-García J, Maccario H, Ciechanover A, Kolch W, Kholodenko BN. PLoS Comput. Biol. 2011 Dec; 7(12): e1002317 Abstract: In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7. This model is hosted on BioModels Database and identified by: BIOMD0000000622. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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RNA-seq and ChIP-seq analysis of BMI1 or RING1B-silenced prostate cancer cells C4-2

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