Tumour suppressor TET2 safeguards enhancers from aberrant DNA methylation and epigenetic reprogramming in ERα-positive breast cancer cells

Lyu, Ruitu; Zhu, Xuguo; Shen, Yinghui; Xiong, Lijun; Liu, Lu; Liu, Huan; Wu, Feizhen; Argueta, Christian; Tan, Li

doi:10.1080/15592294.2021.1997405

Cited by 12 publications

(11 citation statements)

References 51 publications

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“…Moreover, E2/ER promotes TET2 gene transcription in MCF7 cells due to the binding of ERα to 3 ERE upstream of the TET2 gene, suggesting a positive feedback between ERα mediated gene transcriptional activation and TET2-mediated enhancer DNA demethylation. Conversely, our work suggests a tumor-suppressive role of TET2 in ERα+ breast cancer [ 56 ]. In our work, TET2 depletion has no significant effect on the adherent cell growth while promotes the anchorage-independent growth of MCF7 cells.…”

Section: Consequences Of Dysregulated Tet Family Genes and Aberrant 5mc Oxidation In Breast Cancermentioning

confidence: 99%

“…Meanwhile, disrupting the TET2/ERα/GATA3 complex resulted in the dysregulation of cell cycle related gene expression. Our recent work also showed that TET2 loss led to DNA hypermethylation on a large proportion of enhancers including EREs in MCF7 cells [ 56 ]. Consistent to the notion that CpG methylation within EREs impairs ERα binding, our ERα ChIP-seq demonstrated that loss of TET2 impaired the ERα binding and gene transcription of a subgroup of E2-responsive genes in MCF7 cells.…”

Section: Dysregulation Of Tet Family Genes In Breast Cancermentioning

confidence: 99%

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Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Wang

Tan

2021

Cancers

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DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.

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Section: Consequences Of Dysregulated Tet Family Genes and Aberrant 5mc Oxidation In Breast Cancermentioning

confidence: 99%

Section: Dysregulation Of Tet Family Genes In Breast Cancermentioning

confidence: 99%

Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Wang

Tan

2021

Cancers

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“…Coordinates of genomic regions with differential DNA methylation between breast cell lines MCF-10A, MCF-7 and MDA-MB-231 were obtained from (29). Whole-genome bisulfite sequencing in MCF-7 cells reported by (30) was obtained from GSM4055031 in the form of methylation calls in hg19 genome assembly. Coordinates of chromatin domains in breast cells enriched with H3K9me2/3 determined with ChIP-seq by the ENCODE consortium (31) were obtained from the following GEO entries: H3K9me3 in HMEC cells (GSM1003485), H3K9me3 in MCF-7 cells (GSE96517), H3K9me2 in MCF-7 cells (GSE96141).…”

Section: Mnase-seq and Mnase-assisted Histone H3 Chip-seq (Mnase-h3)mentioning

confidence: 99%

“…Calculation of aggregate DNA methylation profiles. We used published bisulfite sequencing data in MCF-7 cells (30), where methylation beta-values per CpG were determined by the authors. NucTools (36) was used to split the regions into chromosomes and 5mC occurrence per CpG was calculated with a cfDNAtools script bed2occupancy.v3d.methyl.pl.…”

Section: Calculation Of Aggregate Occupancy Profilesmentioning

confidence: 99%

Nucleosome reorganisation in breast cancer tissues

Jacob

Guiblet

Mamayusupova

et al. 2023

Preprint

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Nucleosome repositioning in cancer highlights changes of many aspects of genome organisation and regulation. Understanding it is important both from the fundamental point of view and for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. Here we generated ultra-high resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. We detected cancer-specific single-nucleosome repositioning at key regulatory regions in a patient-specific manner, as well as common patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. Tumour tissues were characterised by 5-10 bp decrease in average distances between nucleosomes (nucleosome repeat length, NRL). These effects were modulated by GC content and DNA sequence repeats and correlated with differential DNA methylation and binding of linker histone variants H1.4 and H1X. Our findings provide missing mechanistic understanding of nucleosome positioning in tumour tissues and can be valuable for nucleosomics analyses in liquid biopsies.

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“…In nonsmall cell lung cancer cells, knocking down YBX1 increases the sensitivity of cells to cisplatin by inhibiting autophagy [ 19 ]. In breast cancer, TET2 knockout results in an increase in m5C of most enhancers and a significant reduction in of H3K4me1 and H3K27ac enrichment, which jointly promoted the tumorigenesis of ER α -positive MCF7 breast cancer cells [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

5-Methylcytosine-Related Long Noncoding RNAs Are Potential Biomarkers to Predict Overall Survival and Regulate Tumor-Immune Environment in Patients with Bladder Cancer

Wang

Chen

et al. 2022

Disease Markers

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The role of 5-methylcytosine-related long noncoding RNAs (m5C-lncRNAs) in bladder cancer (BLCA) remains unclear. Here, we aim to study the prognostic value, gene expression characteristics, and correlation between the m5C-lncRNA risk model and the tumor microenvironment, immune infiltration, and tumor mutations in BLCA. After collecting BLCA patient RNA sequence transcriptome data, clinical information and mutation data from the Cancer Genome Atlas (TCGA) database, 17 m5C-related lncRNAs independently correlated with OS were obtained by Lasso and multivariate Cox regression analysis, and a risk model was constructed. Univariate Cox, multivariate Cox regression analysis, and the C-index curve proved that the risk model was a significant independent prognostic indicator for patients with BLCA. ESTIMATE and CIBERSORT indicated that the higher the number of immune cells and stromal cells in TME, the higher the prognostic risk. We found that in the low-risk group, the expression levels of immune cells that predicted a good prognosis were higher, including plasma cells, regulatory T cells, and CD 8 T cells. There is a negative correlation between TMB and risk score. The TMB of the low-risk group is significantly higher than that of the high-risk group. In conclusion, the m5C-related risk model is crucial to predict the prognosis of patients with BLCA.

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Tumour suppressor TET2 safeguards enhancers from aberrant DNA methylation and epigenetic reprogramming in ERα-positive breast cancer cells

Cited by 12 publications

References 51 publications

Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Nucleosome reorganisation in breast cancer tissues

5-Methylcytosine-Related Long Noncoding RNAs Are Potential Biomarkers to Predict Overall Survival and Regulate Tumor-Immune Environment in Patients with Bladder Cancer

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