Project description:The eukaryotic genome is tightly packed inside the nucleus, where it is organized in 3D at different scales. This structure is driven and maintained by different chromatin states and by architectural factors that bind DNA, such as the multi-zinc finger protein CTCF. Zygotic genome structure is established de novo after fertilization, but the impact of such structure on genome function during the first stages of mammalian development is still unclear. Here, we show that deletion of the Ctcf gene in mouse embryos impairs the correct establishment of chromatin structure, but initial lineage decisions take place and embryos are viable until the late blastocyst stage. Furthermore, we observe that maternal CTCF is not necessary for development. Transcriptomic analyses of mutant embryos show that the changes in metabolic and protein homeostasis programs that occur during the progression from the morula to the blastocyst depend on CTCF. Yet, these changes in gene expression do not correlate with disruption of chromatin structure, but mainly with proximal binding of CTCF to the promoter region of genes downregulated in mutants. Our results show that CTCF regulates both 3D genome organization and transcription during mouse preimplantation development, but mostly as independent processes.

2022-10-07 | GSE180306 | GEO

Establishment of 3D chromatin structure after fertilization and the metabolic switch at the morula-to-blastocyst transition require CTCF [Hi-C]

2022-10-07 | GSE180305 | GEO

Project description:O-GlcNAcylation of CTCF regulates 3D chromatin structure

| PRJNA1070848 | ENA

O-GlcNAcylation of CTCF regulates 3D chromatin structure

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

2024-03-04 | GSE255897 | GEO

Nuclear receptor activation leads to functional changes in CTCF-defined chromatin structure [HiChIP]

Project description:The aim of the project was to investigate the effect of nuclear receptor activation, particularly of the vitamin D receptor, on CTCF-defined 3D chromatin structure, and associated functional changes in the transcriptional response of THP-1 cells.

2022-04-27 | GSE188380 | GEO

Chd4 regulates intra-chromatin looping by concealing CTCF sites from B2 SINEs in mESCs

Project description:CTCF plays a critical role in maintaining the three-dimensional (3D) chromatin organization, which is important for gene regulation, as it allows distal regulatory elements to come into proximity with one another. However, the detailed mechanism responsible for establishing and maintaining the recruitment of CTCF remains elusive. Here, we use in situ Hi-C to show that the ATP-dependent chromatin remodeler, Chd4, regulates intra-chromatin looping by controlling chromatin accessibility to conceal aberrant CTCF-binding sites in mouse embryonic stem cells (mESCs). These aberrant CTCF-binding sites are embedded in B2 SINEs and are localized within the interior of chromatin loops. In the absence of Chd4, the aberrant CTCF-binding sites become accessible and improper CTCF recruitment occurs, resulting in disorganization of the 3D chromatin architecture and subsequent disruption of enhancer-promoter interactions and the transcription of the corresponding genes. These results indicate that Chd4 regulates adequate transcription of mESCs by securing the proper 3D chromatin organization.

2022-05-10 | GSE172392 | GEO

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