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Anaphase-promoting complex-dependent control of cell identity

ABSTRACT: Anaphase-promoting complex-dependent control of cell identity

PROVIDER: PRJNA504508 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10074811.fastq.gz	Fastqsanger.gz
	SRR10074812.fastq.gz	Fastqsanger.gz
	SRR10074813.fastq.gz	Fastqsanger.gz
	SRR10074814.fastq.gz	Fastqsanger.gz
	SRR8173531_1.fastq.gz	Fastqsanger.gz

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Anaphase-promoting complex-dependent control of cell identity

Project description:Tissue development and homeostasis rely on the proliferation of progenitor cells, whose identities are established by tightly controlled gene expression networks. However, mRNA synthesis is inhibited during mitosis, and the transcriptional programs that define a cell type must be restarted upon entry into each new cell cycle; how this is accomplished is poorly understood. Here, we identified a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active promoters during interphase, recruit the E3 ligase anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows the APC/C to locally decorate histones with K11/K48-linked ubiquitin chains, which destabilizes nucleosomes and ensures continued gene expression in the next cell cycle. Mitotic exit and transcription re-initiation are therefore controlled by the same essential regulator, the APC/C, which provides a robust mechanism to maintain cell identity through cell division.

2020-02-03 | GSE122298 | GEO

Clinical treatment responsiveness in recurrent canine lymphoma correlates with Anaphase Promoting Complex activity

Project description:Clinical treatment responsiveness in recurrent canine lymphoma correlates with Anaphase Promoting Complex activity

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The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis

Project description:The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis

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Clinical treatment responsiveness in recurrent canine lymphoma correlates with Anaphase Promoting Complex activity

Project description:The development of drug resistant cancer is a chronic threat to those undergoing cancer treatment. Why cells develop resistance to drugs has been studied extensively, with many molecular mechanisms driving the process now understood, yet it remains a chronic problem with few treatment options. In this study we treated companion canines presenting to the Western College of Veterinary Medicine in Saskatoon with drug resistant lymphoma with adjunct metformin along with their normal chemotherapy. We obtained repeated tumor samples from 4 canines undergoing this therapy and assessed RNA obtained from these samples by microarray. We identified a highly interconnected 201 gene set upregulated in the 4 dogs that was associated with tumor progression. This gene set was enriched in genes involved in mitotic progression and chromosome maintenance. We observed that mRNAs encoding substrates of the Anaphase Promoting Complex (APC) were integral to this gene set. Treatment with metformin lowered both protein and RNA levels of these substrates, while relapse resulted in elevated levels once again. The change in APC substrates clearly reflects disease progression, indicating that APC activity is critical for cellular homeostasis and loss of this activity can result in tumor progression.

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The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [lncRNA-seq]

Project description:RNA-directed DNA methylation (RdDM) plays an essential role in transposable element (TE) silencing in plants. In the Arabidopsis RdDM pathway, the DDR complex containing DRD1, DMS3, and RDM1, is necessary for recruiting Pol V to transcribe scaffold RNA. Although the role of DDR is known, the mechanism by which the DDR complex is regulated remains unexplored. Here, we demonstrate that the Anaphase Promoting Complex/Cyclosome (APC/C) monitors the assembly of the DDR complex by targeting DMS3 for degradation. We show that a subset of Pol V-dependent RdDM loci are de-repressed in apc/c mutants, accompanied by defective recruitment and transcription of Pol V. APC/C targets DMS3 for ubiquitination and degradation in a D box-dependent manner, and the D-box-mutated DMS3 fails to complement the dms3 mutant. Competitive binding assays shows that the dosage of DMS3 is critical for the assembly of the DDR complex, and in vivo gel filtration analysis shows that the assembly of both DDR and Pol V is compromised in the apc8 mutant. These findings uncover a safeguard role of APC/C-mediated DMS3 degradation in the assembly of the DDR complex, and provide a direct link between selective protein degradation and RdDM.

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The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [small RNA-seq]

2019-01-31 | GSE106971 | GEO

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Project description:The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [lncRNA-seq]

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Gene expression and cell identity controlled by anaphase-promoting complex.

Project description:Metazoan development requires the robust proliferation of progenitor cells, the identities of which are established by tightly controlled transcriptional networks1. As gene expression is globally inhibited during mitosis, the transcriptional programs that define cell identity must be restarted in each cell cycle2-5 but how this is accomplished is poorly understood. Here we identify a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active interphase promoters6,7, recruit the anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows APC/C to decorate histones with ubiquitin chains branched at Lys11 and Lys48 (K11/K48-branched ubiquitin chains) that recruit p97 (also known as VCP) and the proteasome, which ensures the rapid expression of pluripotency genes in the next cell cycle. Mitotic exit and the re-initiation of transcription are thus controlled by a single regulator (APC/C), which provides a robust mechanism for maintaining cell identity throughout cell division.

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The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [small RNA-seq]

Project description:The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [small RNA-seq]

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Genetic variation in the anaphase promoting complex modulates fertility and chromosome alignment defects in the absence of KIF18A

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