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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [RNA-Seq]

ABSTRACT: The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [RNA-Seq]

PROVIDER: PRJNA1263738 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR33610870_1.fastq.gz	Fastqsanger.gz
	SRR33610870_2.fastq.gz	Fastqsanger.gz
	SRR33610871_1.fastq.gz	Fastqsanger.gz
	SRR33610871_2.fastq.gz	Fastqsanger.gz

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function

Project description:The TET protein family interactor PROSER1 sustains hematopoietic stem cell function

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [Emseq]

Project description:Ten-Eleven-Translocation (TET) enzymes are epigenetic regulators important for prevention of hematological malignancies. PROSER1, a known TET protein interactor, has a critical role in modulating TET-mediated DNA demethylation during development. However, the potential involvement of PROSER1 in regulation of hematopoiesis and leukemogenesis remains unknown. Here, we demonstrate that the leukemia suppressive functions of TET2 are preserved in the absence of PROSER1. Nonetheless, we find that loss of PROSER1 partially recapitulates the aberrant enhancer DNA methylation phenotype observed upon TET2 knockout, suggesting that PROSER1 and TET2 play both cooperative and distinct roles in the regulation of DNA methylation in hematopoiesis. Importantly, using serial hematopoietic stem cell (HSC) transplantation assays, we find progressive exhaustion of HSC activity and reduction in hematopoietic lineage output upon loss of PROSER1. Our findings imply that, beyond the established role of TET2 loss-of-function mutations in promoting HSC expansion and leukemic transformation, accurate TET activity, regulated by PROSER1, is equally important to prevent HSC exhaustion and sustain normal hematopoiesis.

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [ChIP-Seq]

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [RNA-Seq]

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Project description:The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [Emseq]

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [ChIP-Seq]

Project description:The TET protein family interactor PROSER1 sustains hematopoietic stem cell function [ChIP-Seq]

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PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [ChIP-seq]

Project description:The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned – ensuring precise gene expression and developmental fidelity – remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound TET-OGT-PROSER1-DBHS (TOPD) complexes, which regulate DNA demethylation and developmental gene expression. Surprisingly, we find that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element de-repression. Our findings identify PROSER1 as a key factor which both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.

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PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [RNA-seq]

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PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [EM-seq]

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The TET protein family interactor PROSER1 sustains hematopoietic stem cell function

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

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