Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deeply hidden genome organization mediated by base-unpairing regions (BURs) directly bound by SATB1 linked to transcription

ABSTRACT: Mammalian genomes are organized by multi-layered chromatin folding. How three-dimensional genome organization contributes to cell-type specific transcription remains unclear. We uncover genomic elements termed base-unpairing regions (BURs), distributed genome-wide, as the sole and direct targets of cell-type specific SATB1 protein in vivo. The SATB1 direct-binding profile was generated by analyzing stringently-purified genomic DNA crosslinked to its directly-bound proteins only (ureaChIP-seq). Furthermore, a SATB1-bound BUR interacts extensively and frequently over the entire 5.7 megabase gene-rich region within many regulatory regions, including those near SATB1-dependent Rag1/Rag2 genes. SATB1 depletion leads to major loss of these interactions with greatly reduced Rag1/Rag2 expression. Most BURs reside within lamina associated domains (LADs), among which SATB1 binds to cell-type specific groups of BURs. Genome organization mediated by CTCF and SATB1 are distinct as these proteins do not co-bind chromatin in vivo and their direct binding sites are mutually exclusive genome-wide. These results revealed a previously undetected chromatin organization mediated by SATB1 direct binding to selected BURs genome-wide and suggest that chromatin interactions from some of these BURs provide a regulatory network underlying cell-type specific gene expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE191146 | GEO | 2021/12/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

Project description:Rag1 and Rag2 gene expression in CD4+CD8+ double positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. Sequencing of Satb1-ChIP and input control from 6 wk old thymus

2015-02-25 | E-GEOD-66248 | biostudies-arrayexpress

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

2015-02-25 | GSE66248 | GEO

RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2

Project description:The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a PHD finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused, and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused, and dependent on "non-core" portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity, and reveals a novel role for the RAG1 non-core region in RAG1 targeting. ChIP-seq profiles of RAG1 from mouse thymocytes, and H3K27Ac from human REH cell line

2016-07-06 | E-GEOD-84052 | biostudies-arrayexpress

RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2

2016-07-06 | GSE84052 | GEO

The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci

Project description:The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo. Here we demonstrate that RAG protein binding occurs in a highly focal manner to a small region of active chromatin encompassing IgÎº and TcrÎ± J gene segments and Igh and TcrÎ² J and J-proximal D gene segments. Formation of these small RAG-bound regions, which we refer to as recombination centers, occurs in a developmental stage- and lineage-specific manner. Each RAG protein is independently capable of specific binding within recombination centers. While RAG1 binding is restricted to regions containing recombination signal sequences, RAG2 binds extremely broadly in a pattern that mirrors that of trimethylated lysine 4 of histone 3. We propose that recombination centers coordinate V(D)J recombination by providing discrete sites within which gene segments are captured for recombination. RAG2 binding was analyzed in wild type, RAG2-/-Î², and D708A-RAG1-/-Î² thymocytes. Histone modification H3K4me3 was analyzed in D708A-RAG1-/-Î² and wild type thymocytes.

2010-04-19 | E-GEOD-21207 | biostudies-arrayexpress

Deeply hidden genome organization directly mediated by SATB1

Project description:Deeply hidden genome organization directly mediated by SATB1

| PRJNA789873 | ENA

The 3D enhancer network of the developing T cell genome is controlled by SATB1 [Hi-C]

Project description:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of Hi-C and HiChIP experiments is a part of SuperSeries including also RNA-Seq and ATAC-Seq experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. Utilizing the HiChIP data, we compared SATB1 and CTCF-mediated chromatin loops, revealing that SATB1 builds a more refined layer of genome organization upon the CTCF scaffold. Moreover, H3K27ac HiChIP and Hi-C experiments in WT and Satb1 cKO thymocytes helped us to assess the functional impact of SATB1 and its underlying genome-wide regulome. SATB1 primarily mediates promoter-enhancer loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional ubiquitously expressed genome organizers.

2022-09-23 | GSE173446 | GEO

The 3D enhancer network of the developing T cell genome is shaped by SATB1

Project description:Mechanisms of tissue-specific gene expression regulation via 3D genome organization are poorly understood. Here we uncover the regulatory chromatin network of developing T cells and identify SATB1, a tissue-specific genome organizer, enriched at the anchors of promoter-enhancer loops. We have generated a T-cell specific Satb1 conditional knockout mouse which allows us to infer the molecular mechanisms responsible for the deregulation of its immune system. H3K27ac HiChIP and Hi-C experiments indicate that SATB1-dependent promoter-enhancer loops regulate expression of master regulator genes (such as Bcl6), the T cell receptor locus and adhesion molecule genes, collectively being critical for cell lineage specification and immune system homeostasis. SATB1-dependent regulatory chromatin loops represent a more refined layer of genome organization built upon a high-order scaffold provided by CTCF and other factors. Overall, our findings unravel the function of a tissue-specific factor that controls transcription programs, via spatial chromatin arrangements complementary to the chromatin structure imposed by ubiquitously expressed genome organizers.

2022-09-22 | GSE173476 | GEO

The 3D enhancer network of the developing T cell genome is controlled by SATB1 [ATAC-seq]

Project description:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of ATAC-Seq experiments is a part of SuperSeries including also RNA-Seq, Hi-C and HiChIP experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. ATAC-Seq experiments supported the repressive nature of Satb1 cKO nuclear environment and together with the other datasets it showed that SATB1 functions primarily as an activator. SATB1 mediates promoter-enhancer chromatin loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional and ubiquitously expressed genome organizers.

2022-09-23 | GSE173445 | GEO

The 3D enhancer network of the developing T cell genome is controlled by SATB1 [RNA-seq]

Project description:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of RNA-Seq experiments is a part of SuperSeries including also ATAC-Seq, Hi-C and HiChIP experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. RNA-Seq experiments supported the repressive nature of Satb1 cKO nuclear environment and together with the other datasets it showed that SATB1 functions primarily as an activator. SATB1 mediates promoter-enhancer chromatin loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional and ubiquitously expressed genome organizers.

2022-09-23 | GSE173470 | GEO

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