DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38

Dieuleveult, Maud de; Miotto, Benoît

doi:10.1177/2516865718811117

Cited by 19 publications

(17 citation statements)

References 34 publications

(68 reference statements)

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“…We did not observe particular enrichment in GO pathways for APH UP genes (FDR > 0.01). Nevertheless, we noticed an up-regulation of the transcription factor gene ZBTB38 which is a biomarker for prostate cancer (59) and that plays an important role in the regulation of DNA replication, cell cycle and cell fate (60,61). Importantly, the expression of genes that fell inside aRTIL was not affected by low replication stress (Figure 4b).…”

Section: Low Replication Stress Impacts the Regulation Of Genes Involmentioning

confidence: 94%

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Courtot

Bournique

Maric

et al. 2020

Preprint

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DNA replication is very well orchestrated in mammalian cells due to a tight regulation of the temporal order of replication origin activation, known as the replication timing program. The replication timing of a given replication domain is very robust and well conserved in each cell type. Upon low replication stress, the slowing of replication forks induces delayed replication of some fragile regions leading to DNA damage and genetic instability. Except for these fragile regions, the direct impact of low replication stress on the replication timing in different cellular backgrounds has not been explored in detail. Here we analysed DNA replication timing across the whole genome in a panel of human cell lines in the presence of low replication stress. We demonstrate that low replication stress induced by aphidicolin has a stronger impact on the replication timing of cancer cells than non-tumour cells. Strikingly, we unveiled an enrichment of specific replication domains undergoing a switch from late to early replication in some cancer cells. We found that advances in replication timing correlate with heterochromatin regions poorly sensitive to DNA damage signalling while being subject to an increase of chromatin accessibility in response to aphidicolin. Finally, our data indicate that, following release from replication stress conditions, replication timing advances can be inherited by the next cellular generation, suggesting a new mechanism by which some cancer cells would adapt to cellular or environmental stress.

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Section: Low Replication Stress Impacts the Regulation Of Genes Involmentioning

confidence: 94%

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Courtot

Bournique

Maric

et al. 2020

Preprint

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“…It suggests that monitoring ZBTB38 SNP and mRNA status might improve the diagnosis and care of prostate cancer patients. The development of immunochemistry assays to monitor ZBTB38 protein levels in prostate specimens might also be valuable, as the protein is tightly regulated by ubiquitination [31,32,40], and its cellular abundance may differ from its mRNA expression.…”

Section: Zbtb38 and Its Paralogs Zbtb4 And Kaiso/zbtb33 Are Involved In Prostate Cancermentioning

confidence: 99%

“…In bladder cancer cells, ZBTB38 promotes cell migration and invasion, in part, by regulating Wnt/β-catenin signalling [38]. It was also showed that down-regulation of ZBTB38 potentiates the efficacy of anti-cancer DNA demethylating agent 5-azacytidine while causing heightened levels of reactive oxygen species (ROS) [32,33,40]. Interestingly, association between prostate cancer risk and ROS levels has been observed and it is thought that ROS contribute to the development and progression of the disease [41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer

Dieuleveult

Marchal

Jouinot

et al. 2020

Cancers

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Prostate cancer is one of the most commonly diagnosed cancers in men. A number of genomic and clinical studies have led to a better understanding of prostate cancer biology. Still, the care of patients as well as the prediction of disease aggressiveness, recurrence and outcome remain challenging. Here, we showed that expression of the gene ZBTB38 is associated with poor prognosis in localised prostate cancer and could help discriminate aggressive localised prostate tumours from those who can benefit only from observation. Analysis of different prostate cancer cohorts indicates that low expression levels of ZBTB38 associate with increased levels of chromosomal abnormalities and more aggressive pathological features, including higher rate of biochemical recurrence of the disease. Importantly, gene expression profiling of these tumours, complemented with cellular assays on prostate cancer cell lines, unveiled that tumours with low levels of ZBTB38 expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that ZBTB38 is involved in prostate cancer pathogenesis and may represent a useful marker to identify high risk and highly rearranged localised prostate cancer susceptible to doxorubicin.

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“…ZBTB38, also known as CIBZ (CtBP-interacting BTB zinc finger protein), is another member of the BTB-ZF family and can function either as a transcriptional repressor or activator [ 14 ]. In contrast to other BTB-ZF factors that bind to similar DNA sequences, ZBTB38-mediated transcriptional regulation occurs by binding primarily to specific methylated CpG sequences and recruiting repressors or activators [ 15 – 19 ]. The uniqueness of ZBTB38 binding sites relative to other BTB-POZ factors led us to speculate that this factor would have a functionally important and non-redundant role in B cell responses.…”

Section: Introductionmentioning

confidence: 99%

ZBTB38 is dispensable for antibody responses

Wong

Bhattacharya

2020

PLoS ONE

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Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion of Zbtb38 showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.

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DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38

Cited by 19 publications

References 34 publications

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer

ZBTB38 is dispensable for antibody responses

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