Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation

ABSTRACT: During mammalian embryogenesis, both the 5-cytosine DNA methylation (5meC) landscape and three dimensional (3D) chromatin architecture are profoundly remodeled during a process known as 'epigenetic reprogramming.' An understudied aspect of epigenetic reprogramming is how the 5meC flux, per se, affects the 3D genome. This is pertinent given the 5meC-sensitivity of DNA binding for a key regulator of chromosome folding: CTCF. We profiled the CTCF binding landscape using a mouse embryonic stem cell (ESC) differentiation protocol that models embryonic 5meC dynamics. Mouse ESCs lacking DNA methylation machinery are able to exit naive pluripotency, thus allowing for dissection of subtle effects of CTCF on gene expression. We performed CTCF HiChIP in both wild-type and mutant conditions to assess gained CTCF-CTCF contacts in the absence of 5meC. We performed H3K27ac HiChIP to determine the impact that ectopic CTCF binding has on cis-regulatory contacts. Using 5meC epigenome editing, we demonstrated that the methyl-mark is able to impair CTCF binding at select loci. Finally, a detailed dissection of the imprinted Zdbf2 locus showed how 5meC-antagonism of CTCF allows for proper gene regulation during differentiation. This work provides a comprehensive overview of how 5meC impacts the 3D genome in a relevant model for early embryonic events.

ORGANISM(S): Mus musculus

PROVIDER: GSE246984 | GEO | 2024/07/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

X-chromosome dynamics revealed by the RNA interactome and chromosomal binding of CTCF

Project description:CTCF is a master regulator that plays a role in genome architecture and gene expression. A key aspect of CTCF’s mechanism involves bringing together distant genetic elements for intra- and inter-chromosomal interactions. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), suggests that CTCF may carry out its functions through interacting RNAs. Using genome-wide approaches to investigate the relationship between CTCF’s RNA interactome and its epigenomic landscape, here we report that CTCF interacts with thousands of transcripts in mouse embryonic stem cells (mESC), many in close proximity to CTCF’s genomic binding sites. Biochemical analysis demonstrates that CTCF is a high-affinity RNA binding protein that contacts RNA directly and specifically. In the XCI model, CTCF binds the active and inactive X-chromosomes allele-specifically. At the X-inactivation center, Tsix RNA binds CTCF and targets CTCF to a region associated with X-chromosome pairing. Our work implicates CTCF-RNA interactions in long-range chromosomal interactions in trans and adds a new layer of complexity to CTCF regulation. The genome-wide datasets reported here will provide a useful resource for further study of CTCF-mediated epigenomic regulation. CTCF RNA interactome was identified by UV-crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq), and was compared to CTCF's epigenomic landscape as obtained by chromatin immunoprecipitation (ChIP-seq).

2015-01-09 | E-GEOD-58242 | biostudies-arrayexpress

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [bisulfite-seq]

Project description:Early mammalian development is accompanied by a profound global remodeling of chromatin-based regulation. The Zdbf2 locus provides a valuable model to uncover the effect of dynamic chromatin transition, as it is polycomb silenced in embryonic stem cells (ESCs) and only becomes activated after Long isoform of Zdbf2 (Liz) transcription-dependent de novo DNA methylation during differentiation. Here we show that four enhancers contribute to the Liz-to-Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. CTCF plays a key role in partitioning the locus in ESCs, when Liz is active and Zdbf2 is silenced. The partition is relieved when Zdbf2 becomes DNA methylated and active. Mutant ESCs that lack the partition fail to properly activate Zdbf2. Notably, the CTCF-based regulation occurs independently of the polycomb and DNA methylation pathways, suggesting a multi-layered regulatory framework that ensures proper epigenetic programming of a developmentally important gene.

2019-04-18 | GSE121402 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [ATAC-Seq]

2019-04-18 | GSE121400 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [4C-Seq]

2019-04-18 | GSE121399 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [RNA-Seq]

2019-04-18 | GSE121403 | GEO

Cohesin HiChIP datasets of pluripotent and surface ectoderm cells with and without p63

Project description:Purpose: Assess changes in the three-dimensional (3D) chromatin architecture during surface ectoderm commitment and evaluate changes in 3D chromatin architecture in human embryonic stem cells and surface ectoderm cells with and without p63. Methods: Cohesin HiChIP profiles for human embryonic stem cells and surface ectoderm cells with and without p63 were generated in triplicate with deep sequencing on the Illumina HiSeq 4000 sequencer. Using HiC-Pro, paired end reads were aligned to hg19, duplicate reads were removed, and then were assigned to MboI restriction fragments, filtered for valid interactions, and used to generate binned interaction matrices of 10 kb resolution. Contacts were called using FitHiC and filtered for counts >= 10 and FDR < 0.001. Results: The greatest change in 3D chromatin architecture was observed between human embryonic stem cells and surface ectoderm cells, while moderate changes were observed in human embryonic stem cells with and without p63, and limited changes were observed in surface ectoderm cells with and without p63. Conclusion: Both p63 and the surface ectoderm morphogens direct changes in chromatin folding to establish the 3D chromatin landscape in the surface ectoderm.

2018-11-06 | GSE120294 | GEO

Systematic mapping of 3D enhancer interactions reveals lineage specific regulatory networks during early mouse developmental decisions [4C-Seq]

Project description:To model and characterize the chromatin regulatory landscape of the very first developmental cell fates, we made use of three previously derived and well-characterized Trophoblast Stem Cell (TSCs), Embryonic Stem Cell (ESC) and Extra Embryonic Stem Cell lines (XENs) We performed high-resolution in situ 4C-seq analysis around enhancers and promoters of cell-type specific genes (e.g. Sox17 for XEN and Nanog for ESC), which showed high concordance both with the virtual 4C of HiChIP and the called HiChIP contacts in the respective cell type

2023-08-21 | GSE212992 | GEO

Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation (Hi-C)

Project description:Transcriptional reprogramming during cell fate determination involves precise targeting of enhancers to tissue-specific genes. Enhancer-promoter interactions are regulated by different types of 3D chromatin organization, including compartmental domains and CTCF loops. To understand the contribution of these different levels of chromatin organization in cell lineage commitment, we analyzed changes in 3D organization during the differentiation of human embryonic stem cells (hESCs) into pancreatic islet organoids. We find that major events in chromatin reorganization, including decompaction of transposon-enriched heterochromatin, breakdown of poised enhancer-promoter interaction networks, gain or loss of CTCF loops and establishment of novel enhancer-promoter contacts, occur either sequentially or simultaneously. Transcriptionally activated transposons released from unstable heterochromatin compartments recruit CTCF to form new loops. In contrast, when released from poised long-range interaction networks, enhancers and genes crucial for cell differentiation recruit tissue-specific transcription factors by either direct binding or indirect 3D contacts containing RNA Polymerase II. Activation of stage-specific genes correlates with gain of CTCF binding at anchors of extended CTCF loops, suggesting changes in loop extrusion capacity. In agreement with this, we find a global increase in cohesin loading leading to longer residency on extended CTCF loops encompassing tissue-specific genes. Our findings provide new insights into how distinct types of chromatin organization affect the reprogramming of gene expression patterns to regulate cell lineage commitment.

2023-09-19 | GSE210524 | GEO

Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation (Hi-ChIP)

2023-09-19 | GSE210525 | GEO

Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation

2023-09-19 | GSE211101 | GEO