Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation [RNA-seq]

ABSTRACT: In mouse embryonic stem cells (mES cells), ubiquitylation of histone H2A lysine 119 represses a large number of developmental genes and maintains mES cell pluripotency. It has been suggested that a number of H2A ubiquitin ligases as well as deubiquitylases and related peptide fragments contribute to a delicate balance between self-renewal and multi-lineage differentiation in mES cells. Here, we tested whether known H2A ubiquitin ligases and deubiquitylases are involved in mES cell regulation and discovered that Dzip3, the E3 ligase of H2AK119, represses differentiation-inducible genes as well as Ring1B. The two sets of target genes partially overlapped but had different spectra. We found that Dzip3 represses gene expression by orchestrating changes in 3D organization in addition to regulating ubiquitylation of H2A. Our results shed light on the epigenetic mechanism of transcriptional regulation, which depends on 3D chromatin reorganization to regulate mES cell differentiation. mouse ES cell mRNA profiles of control, Ring1B knock down, and Dzip3 knock down, in duplicate, using Illumina MiSeq.

ORGANISM(S): Mus musculus

SUBMITTER: Daishi Inoue

PROVIDER: E-GEOD-71882 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation.

Inoue Daishi D Aihara Hitoshi H Sato Tatsuharu T Mizusaki Hirofumi H Doiguchi Masamichi M Higashi Miki M Imamura Yuko Y Yoneda Mitsuhiro M Miyanishi Takayuki T Fujii Satoshi S Okuda Akihiko A Nakagawa Takeya T Ito Takashi T

Scientific reports 20151116

In mouse embryonic stem (mES) cells, ubiquitylation of histone H2A lysine 119 represses a large number of developmental genes and maintains mES cell pluripotency. It has been suggested that a number of H2A ubiquitin ligases as well as deubiquitylases and related peptide fragments contribute to a delicate balance between self-renewal and multi-lineage differentiation in mES cells. Here, we tested whether known H2A ubiquitin ligases and deubiquitylases are involved in mES cell regulation and disco ...[more]

PMID: 26568260

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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.

Dataset Information

Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation [RNA-seq]

Publications

Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation.

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