Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

ABSTRACT: Homeobox B cluster (HoxB) genes play important roles in RA-induced early ESCs differentiation. In this study, we identified two enhancers synergistically regulate HoxB genes expressions through 3D chromatin structure and thus regulate RA-induced early ESCs differentiation. 4C data showed interactions between HoxB genes and the two enhancers. CRISPR/Cas9-mediated individual or compound deletion of the two enhancers significantly inhibits HoxB genes expressions while transcriptome analysis revealed that RA induced early ESCs differentiation was blocked in the enhancer KO cells. Our study suggests new mechanism by which two enhancers regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure.

ORGANISM(S): Mus musculus

PROVIDER: GSE165725 | GEO | 2021/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

Project description:Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

| PRJNA695544 | ENA

RA-dependent proximal and distal enhancers’ architecture promotes RA-induced early ESC differentiation

Project description:Retinoic acid (RA) plays a pivotal role in different biological processes including inducing differentiation of embryonic stem cells (ESCs). We first knocked out one or both of RA receptors- Rarα and Rxrα to partially abolish the RA signaling, and then overexpressed one of them separately to hyper activation of RA signaling pathway. By transcriptome analysis, we show that RA signaling effects multi-lineage differentiation, particularly the endoderm, and identify RA signaling target genes, interesting, there are two family cluster genes- Hoxb and Cyp26. Chromosome immunoprecipitation (ChIP-seq) shows that RA induces novel proximal and distal enhancers around the cluster target genes and these enhancers are dependent of RA receptors(Rarα/Rxrα). 4C-seq reveals enhancer-enhancer and enhancer-promoter interactions in their regions and shows a decrease in the relative frequency of contact relative to WT after Rarα/Rxrα-knockout, suggesting Rarα/Rxrα participate in mediating chromatin interaction. We also identify that enhancers significantly maintain expression of RA-induced Hoxb and Cyp26 family genes and regulate multi-lineage marker genes. At the same time, we reveal that disrupting RA-response elements (RAREs) in the enhancer affects the expression of the target gene. Our study provides mechanistic insight into RA-induced early ESC differentiation to endoderm and potential regular regulation of downstream target genes.

2023-06-29 | GSE221992 | GEO

A CTCF binding element regulates RA-induced early ESCs differentiation through orchestrating long-range chromatin interactions between its adjacent enhancers and HoxA

Project description:Proper Homeobox A (HoxA) cluster genes expression is essential for embryonic stem cells (ESCs) differentiation and individual development. However, the mechanisms controlling the precise spatiotemporal expression of HoxA cluster genes during early ESCs differentiation remain largely unknown. Here, we find a CTCF binding element (CBE+47kb) closest to the 3'-end of HoxA locus within a topologically associated domains (TAD) in ESCs. CRISPR-Cas9 mediated the CBE+47kb knockout significantly promotes expression of HoxA cluster genes and early ESCs differentiation induced by RA compared with wild type cells. In mechanism, we found that there was a significant differently long-range chromatin interactions between its adjacent enhancers and HoxA in CBE+47kb knockout cells through chromosome conformation capture assay (Capture-C), indicating that CBE+47kb can precisely organize interactions between its adjacent enhancers and HoxA chromatins. Furthermore, we also showed that its adjacent enhancers deletion shows significantly synthetic inhibition effect on HoxA genes expression, suggesting that these enhancers are required for RA-induced HoxA genes expression. Our study reveals that a new functional CBE+47 can regulate HoxA genes expression through orchestrating long-range chromatin interactions between its adjacent enhancers and HoxA, thus maintaining RA-induced early ESCs proper differentiation.

2020-07-16 | GSE154495 | GEO

A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation

Project description:Retinoic acid (RA) induces rapid differentiation of ESCs, partly by activating expression of the transcription factor Hoxa1, which regulates downstream target genes that promote ESCs differentiation. However, mechanisms of RA-induced Hoxa1 expression and ESCs early differentiation remain largely unknown. Here, we identify a distal enhancer interacting with the Hoxa1 locus through a long-range chromatin loop. Enhancer deletion significantly inhibited expression of RA-induced Hoxa1 and endoderm master control genes such as Gata4 and Gata6. Transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in Hoxa1 enhancer knockout cells, suggesting a requirement for the enhancer. Restoration of Hoxa1 expression partly rescued expression levels of ~40% of genes whose expression changed following enhancer deletion, and ~18% of promoters of those rescued genes were directly bound by Hoxa1. Our data show that a distal enhancer maintains Hoxa1 expression through long-range chromatin loop and that Hoxa1 directly regulates downstream target gene expression and then orchestrates RA-induced early differentiation of ESCs.

2018-12-24 | GSE124306 | GEO

Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signal-induced early differentiation of ESC

Project description:Signaling pathway driven target gene transcriptions are critical for fate determination of embryonic stem cells (ESC), but enhancer architecture-dependent transcriptional regulation remains largely unclear in this process. Here, we described a complex enhancer architecture-dependent multilayered transcriptional regulation that orchestrates retinoic acid (RA) signal-induced early differentiation of ESC. Specifically, we identified Hoxa1 and lncRNA Halr1 as the direct downstream target genes of RA signal. Chromosome conformation capture based screens show that increased enhancer interactions promoted by RA signal are essential for Hoxa1 and Halr1 expressions during early ESC differentiation. Furthermore, we find that HOXA1 promotes Halr1 expression through direct binding to enhancers; conversely, absence of Halr1 RNA enhances interaction between Hoxa1 chromatin and multiple enhancers, but weakens interaction with HoxA cluster internal chromatin, thereby promoting RA signal-induced Hoxa1 overactivation and early differentiation of ESC. These results indicate that Halr1 binds to chromatin not only acts as a brake to orchestrate interaction between enhancers and Hoxa1 chromatin, but also acts as a binder to maintain chromatin interaction within HoxA cluster. In summary, these findings reveal a complex multilayered transcriptional regulation involving the synergistic regulation of enhancer, transcription factor and lncRNA, and that increases our understanding of the intrinsic molecular mechanisms of RA signal-induced ESC differentiation.

2021-04-16 | GSE169058 | GEO

An essential role for UTX in resolution and activation of bivalent promoters

Project description:In the present study, we show that UTX plays an essential role in resolving and activating many retinoic acid (RA)-inducible bivalent genes during the RA-driven differentiation of mouse ESCs treated with a physiologically relevant RA concentration (0.2 μM). We showed that UTX loss and UTX knockdown interfered with the RA-induced differentiation of mouse ESCs. Therefore, our findings indicate that the UTX-mediated resolution and activation of many RA-inducible bivalent genes, including numerous Hoxa-d cluster genes, are required for RA-driven differentiation of mouse ESCs.

2016-02-05 | GSE76692 | GEO

An essential role for UTX in resolution and activation of bivalent promoters

Project description:In the present study, we show that UTX plays an essential role in resolving and activating many retinoic acid (RA)-inducible bivalent genes during the RA-driven differentiation of mouse ESCs treated with a physiologically relevant RA concentration (0.2 Î¼M). We showed that UTX loss and UTX knockdown interfered with the RA-induced differentiation of mouse ESCs. Therefore, our findings indicate that the UTX-mediated resolution and activation of many RA-inducible bivalent genes, including numerous Hoxa-d cluster genes, are required for RA-driven differentiation of mouse ESCs. ChIP-Seq data for H3K4me3 and H3K27me3 were generated along with input data for mouse stem cells with wild type or UTX-depleted genotype and with or without RA treatment.

2016-02-05 | E-GEOD-76692 | biostudies-arrayexpress

Genome-wide quantitative functional enhancer map of mESCs, in the pluripotent state and after induced differentiation

Project description:Precise spatiotemporally regulated gene expression is pivotal for cell homeostasis, cell differentiation and during development. Gene expression networks are tightly regulated by transcription factors (TF) and their targeted regulatory genomic elements (enhancers), which are known to correlate with specific histone modifications. However, the ultimate prerequisites, which determine functionally active enhancers, remain unclear. To elucidate the regulatory landscape of murine ESCs, a massively parallel reporter assay, based on STARR-seq (Self-Transcribing Active Regulatory Region sequencing), assessing genomic fragments prepared from accessible chromatin, (FAIRE-STARR-seq) has been applied. Thus, a genome-wide quantitative map of functional mESC enhancers in naive state and after retinoic acid (RA)-induced differentiation was generated. To investigate sequence features associated with RA-mediated inducibility of enhancers bound by retinoic acid receptor alpha (RARα), the main receptor for RA, genomic binding sites of RARα have been determined.

2021-10-21 | GSE171771 | GEO

KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure

Project description:Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation, such as Pax6. Combination analysis employing ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers. And changes of chromatin structure upregulated expression of neural differentiation-associated genes and promoted early neural differentiation. This study reveals that KLF4 has a differentiation inhibitory effect in regulating 3D chromatin structure and suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.

2022-06-01 | GSE194068 | GEO

A CTCF binding element regulates RA-induced early ESCs differentiation through orchestrating long-range chromatin interactions between its adjacent enhancers and HoxA

Project description:A CTCF binding element regulates RA-induced early ESCs differentiation through orchestrating long-range chromatin interactions between its adjacent enhancers and HoxA

| PRJNA646489 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data