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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions

ABSTRACT: TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions

PROVIDER: PRJNA641866 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12090700.fastq.gz	Fastqsanger.gz
	SRR12090800.fastq.gz	Fastqsanger.gz
	SRR12090900.fastq.gz	Fastqsanger.gz
	SRR12091000.fastq.gz	Fastqsanger.gz
	SRR12091100.fastq.gz	Fastqsanger.gz

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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions

Project description:Estrogen receptor-alpha (ER) drives tumour development and metastasis in ER positive (ER+) breast cancer. GATA3 is a transcription factor that has been closely linked to ER function, but the role of GATA3 in ER-transcriptional activity is not clear. We sought to identify the contribution of GATA3 to the ER complex, by conducting quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME), to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, very few proteins were dissociated from the ER complex in the absence of GATA3, with the only major change being loss of TET2 in the ER complex. In breast cancer cells and Patient-Derived Xenograft (PDX) tissue, TET2 binding events were shown to constitute a near-total subset of ER binding events, and loss of TET2 was functionally associated with reduced activation of proliferative pathways. To investigate the TET2-ER relationship, the role of TET2 in regulating DNA modifications in ER+ breast cancer cells was examined. TET2 knockdown did not appear to result in changes to global DNA methylation, however, oxidation of methylated DNA to 5-hydroxymethylcytosine (5hmC) was significantly reduced after TET2 depletion and these events occurred at ER enhancers. These findings implicate TET2 in the production and maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.

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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [MMS/RRHP]

Project description:Estrogen receptor-a (ER) drives tumour development and metastasis in ER positive (ER+) breast cancer. GATA3 is a transcription factor that has been closely linked to ER function, but the role of GATA3 in ER transcriptional activity is not clear. We sought to identify the contribution of GATA3 to the ER complex by conducting quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME) to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, very few proteins were dissociated from the ER complex in the absence of GATA3, with the only major change being depletion of TET2 from the ER complex. In breast cancer cells and Patient-Derived Xenograft (PDX) tissue, TET2 binding events were shown to constitute a near-total subset of ER binding events, and loss of TET2 was functionally associated with reduced activation of proliferative pathways. To investigate the TET2-ER relationship, the role of TET2 in regulating DNA modifications in ER+ breast cancer cells was examined. TET2 knockdown did not appear to result in changes to global DNA methylation, however, oxidation of methylated DNA to 5-hydroxymethylcytosine (5hmC) was significantly reduced after TET2 depletion and these events occurred at ER enhancers. These findings implicate TET2 in the production and maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.

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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [RNA-Seq]

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Project description:TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [MMS/RRHP]

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Project description:TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [ChIP-Seq]

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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [RNA-Seq]

Project description:TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions [RNA-Seq]

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Project description:Estrogen receptor-α (ER) drives tumor development in ER-positive (ER+) breast cancer. The transcription factor GATA3 has been closely linked to ER function, but its precise role in this setting remains unclear. Quantitative proteomics was used to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, few proteins were lost from the ER complex in the absence of GATA3, with the only major change being depletion of the dioxygenase TET2. TET2 binding constituted a near-total subset of ER binding in multiple breast cancer models, with loss of TET2 associated with reduced activation of proliferative pathways. TET2 knockdown did not appear to change global methylated cytosine (5mC) levels; however, oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) was significantly reduced, and these events occurred at ER enhancers. These findings implicate TET2 in the maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.

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TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions

Project description:This SuperSeries is composed of the SubSeries listed below.

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