Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ChIP-seq to measure binding of NIPBL/MAU2, RAD21, and CTCF in mouse embryonic stem cells and neural progenitor cells

ABSTRACT: Mammalian chromosomes are folded by the cohesin complex, which creates chromatin loops that are extruded as cohesin translocates along the chromatin fiber. This dynamic process regulates gene expression by controlling the frequency of contacts between enhancers and promoters. We analyzed where in the genome loop extrusion occurs to discover where extrusion initiates and whether particular regions are extruded more than others. We measured NIPBL/MAU2 binding in mouse embryonic stem cells and neural progenitor cells, and found that NIPBL/MAU2 is enriched at enhancers compared to promoters. We used the amount of cohesin binding at CTCF sites as a readout of cohesin traffic, and found that the NIPBL/MAU2 binding sites only modestly boost nearby cohesin levels.

ORGANISM(S): Mus musculus

PROVIDER: GSE278338 | GEO | 2025/09/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers

Project description:While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not well understood. Recently, we and others have proposed that direct interactions with transcription factors (TFs) lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of protein-protein interaction (PPI) motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs. These PPIMs directly interact with chromatin-associated proteins, including TFs and one of them is necessary for the maintenance of the NIPBL-MAU2 heterodimer. Finally, using the glucocorticoid receptor (GR) as a model, we investigate its interaction surfaces with NIPBL and MAU2 using AlphaFold2 and surface plasmon resonance to uncover a TF-NIPBL-MAU2 ternary complex and present its importance in GR-dependent gene regulation.

2025-04-17 | PXD058574 | Pride

MAU2 and NIPBL variants in Cornelia de Lange syndrome reveal MAU2-independent loading of cohesin and uncover protective mechanisms against early truncating mutations in NIPBL

Project description:For its association with chromatin, the cohesin complex depends on a heterodimer formed by NIPBL and MAU2. Variants in NIPBL are the main cause of CdLS and result in NIPBL haploinsufficiency. Using CRISPR, we generated cells homozygous for an out-of-frame duplication in NIPBL. Remarkably, alternative translation initiation rescued NIPBL expression in these cells and produced an N-terminally truncated NIPBL that lacks MAU2-interaction domain, causing a dramatic reduction of MAU2 protein levels while a lot of NIPBL functions remain intact.

2020-06-10 | GSE122299 | GEO

Transcription Factors Form a Ternary Complex with NIPBL/MAU2 to Localize Cohesin at Enhancers

Project description:The cohesin complex is a key player in dynamic genome architecture adjustments. The loading of the cohesin complex on chromatin is believed to be achieved by the cohesin-loader Nipped-B homolog (NIPBL). Recently, we and others proposed that direct interactions with transcriptions factors (TFs) would lead to accurate positioning of NIPBL on the DNA. In this study, we identified remarkable protein-protein interaction motifs (PPIMs) in the NIPBL sequence. Mutations of those motifs dramatically alters: (i) the global NIPBL chromatin binding, (ii) the NIPBL-dependent transcriptional program and (iii) the NIPBL proteome network including TFs. While we found that the MAU2/NIPBL interaction was relying on those PPIMs, we further discovered that MAU2 was directly interacting with dozens of TFs. Concomitantly, we found that numerous TFs were also able to interact with NIPBL through PPIMs. Finally, using nuclear receptors as models and then focusing on the Glucocorticoid Receptor (GR), we mechanistically dissect a trimeric complex formed by GR, NIPBL and MAU2 and investigate the importance of those interactions for GR transcriptional program.

2025-04-16 | GSE282583 | GEO

Calcium Signaling Prompts NIPBL Recruitment at Active Enhancers and Promoters via Distinct Mechanisms to Reconstruct Genome Compartmentalization

Project description:During developmental progression the genomes of immune cells undergo large-scale changes in chromatin folding. However, insights into the signals and epigenetics that induce alterations in nuclear architecture remain rudimentary. Here, we found that calcium influx rapidly recruited the cohesin-loading factor NIPBL to thousands of binding sites to dictate widespread changes in compartment segregation. The induction of NIPBL-binding was coordinate with increased P300, BRG1 and RNA Polymerase II co-occupancy, via different kinetics at active enhancers and promoters. Through acute degradation system, we found that enhancers, rather than promoters, are dependent on BAF complexes to induce NIPBL recruitment. Finally, we found that calcium signaling acts universally to orchestrate rapid redistribution of NIPBL in both primary innate and adaptive immune cells. Collectively, these data reveal how calcium signaling regulates NIPBL occupancy to orchestrate nuclear architecture.

2020-10-10 | GSE154051 | GEO

Nuclear Morphology is Instructed by the Loop Extrusion Program [ChIP-Seq]

Project description:More than a century ago Metchnikoff defined neutrophils as small amoeboid-like cells that harbored peculiar polymorphonuclear structures. While since these early studies much has been learned about neutrophil physiology, mechanistic insight into neutrophil polymorphonuclear assembly remains rudimentary. Here we found that depletion of factors, that initiate the loop extrusion program, including NIPBL and MAU2, greatly accelerated the conversion of mononuclear to polymorphonuclear cells and orchestrated the induction of a neutrophil specific transcription signature. Remarkably, mere ablation of either NIPBL or MAU2 expression under conditions that normally prevent neutrophil differentiation, swiftly converted mono-nuclear into polymorphonuclear cells that expressed a neutrophil specific gene program. Depletion of NIPBL and MAU2 in neutrophil progenitors activated an armamentarium of neutrophil-specific enhancers to establish a neutrophil genome depleted for loop extrusion-induced looping. These observations indicate that extinction of the loop extrusion program converts mononuclear progenitor cells into polymorphonuclear cells and suffices to induce a neutrophil specific program of gene expression.

2024-02-11 | GSE235645 | GEO

Nuclear Morphology is Instructed by the Loop Extrusion Program [scRNA-seq]

2024-02-11 | GSE211819 | GEO

Nuclear Morphology is Instructed by the Loop Extrusion Program [ATAC-Seq]

2024-02-11 | GSE211817 | GEO

Nuclear Morphology is Instructed by the Loop Extrusion Program [HiC]

2024-02-11 | GSE232064 | GEO

Transcription Factors Recruit the Cohesin Loader NIPBL to Promote Chromatin Looping and Long-range Gene Regulation

Project description:The cohesin complex is central to chromatin looping, but mechanisms by which these long-range chromatin interactions are formed and persist remain unclear. We demonstrate that interactions between a transcription factor and the cohesin loader NIPBL regulate enhancer-promoter looping and promote long-range gene regulation. Using mass-spectrometry, genome mapping, and single-molecule tracking methods, we demonstrate that NIPBL and cohesin regulate the dynamics and function of the glucocorticoid receptor (GR). Moreover, glucocorticoid treatment stabilizes NIPBL and cohesin interactions by promoting loop extrusion and chromatin looping. Patient-derived acute myeloid leukemia cells harboring cohesin mutations exhibit a reduced response to glucocorticoids (GCs), suggesting that the GR-NIPBL-cohesin interaction is defective in these patients, and they may be poor candidates for GC treatment.

2021-06-01 | GSE162617 | GEO

Nuclear Morphology is Instructed by the Loop Extrusion Program [RNA-seq]

2024-02-11 | GSE211818 | GEO