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Identification of the key epigenetic determinants of chondrocyte aging in humans (Cut&Run)

ABSTRACT: Identification of the key epigenetic determinants of chondrocyte aging in humans (Cut&Run)

PROVIDER: PRJNA751618 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15328364_1.fastq.gz	Fastqsanger.gz
	SRR15328364_2.fastq.gz	Fastqsanger.gz
	SRR15328365_1.fastq.gz	Fastqsanger.gz
	SRR15328365_2.fastq.gz	Fastqsanger.gz
	SRR15328366_1.fastq.gz	Fastqsanger.gz

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Identification of the key epigenetic determinants of chondrocyte aging in humans

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Identification of the key epigenetic determinants of chondrocyte aging in humans (Cut&Run)

Project description:Articular chondrocytes undergo functional changes and their regenerative potential declines with age. Although the molecular mechanisms guiding articular cartilage aging is poorly understood, DNA methylation is known to play a mechanistic role in aging. However, our understanding of DNA methylation in chondrocyte development across human ontogeny is limited. To better understand DNA methylome changes, methylation profiling was performed in human chondrocytes. This study reveals association between methylation of specific CpG sites and chondrocyte age. We also determined the putative binding targets of STAT3, a key age-patterned TF in fetal chondrocytes and genetic ablation of STAT3 induced a global genomic hypermethylation. Moreover, an epigenetic clock built for adult human chondrocytes revealed that exposure of aged adult human chondrocytes to STAT3 agonist, decreased epigenetic age. Taken together, this work will serve as a foundation to understand development and aging of chondrocytes with a new perspective for development of rejuvenation agents for synovial joints.

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Demonstration of CUT&RUN motif footprint analysis using key blood progenitor transcription factors

Project description:We introduce CUT&RUNTools (https://bitbucket.org/qzhudfci/cutruntools/) as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&RUN primary cleavage data. CUT&RUNTools extracts endonuclease cut site information from sequences of short read fragments and produces single-locus binding estimates, aggregate motif footprints, and informative visualizations to support the high-resolution mapping capability of CUT&RUN. We illustrate the functionality of CUT&RUNTools through analysis of CUT&RUN data acquired for GATA1, a master regulator in erythroid lineage cells. Results were compared initially to published GATA1 ChIP-seq data for cells under the same conditions. We performed de novo analysis of CUT&RUN peaks to retrieve not only GATA1’s primary motif, but also the GATA1-TAL1 composite motif, and co-factor motifs GCCCCGCCTC, CMCDCCC, and RTGASTCA that correspond to SP1, KLF1, and NFE2 co-factors. Cofactor binding was verified by independent TAL1 and KLF1 CUT&RUN, and other ChIP-seq experiments. CUT&RUNTools also generated base-pair resolution motif footprint for sequence-specific binding factors, and located likely direct binding sites by quantifying log-odds of binding scores. Overall, CUT&RUNTools should enable biologists to realize advantages of cleavage data provided by CUT&RUN, and make high-quality footprinting analysis accessible to a broad audience.

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Identification of the key epigenetic determinants of chondrocyte aging in humans

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

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