Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA100953 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The human body is composed of diverse cell types with distinct functions. While it is known that lineage specification depends on cell specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1-3, the relative roles of these regulatory elements in this process is not clear. We have previously developed a chromatin immunoprecipitation-based microarray method (ChIP-chip) to identify promoters, enhancers and insulator elements in the human genome4-6. Here, we use the same approach to identify these active elements in multiple cell types and investigated their roles in cell type-specific gene expression. We observed that chromatin state at promoters and CTCF-binding at insulators are largely invariant across diverse cell types. By contrast, enhancers are marked with highly cell type-specific histone modification patterns, strongly correlate to cell type-specific gene expression programs on a global scale, and are functionally active in a cell type-specific manner. Our results defined over 55, 000 potential transcriptional enhancers in the human genome, significantly expanding the current catalog of human enhancers and highlighting the role of these elements in cell type-specific gene expression. Keywords: ChIP-chip
2009-03-01 | GSE14083 | GEO
Project description:Characterisation of different histone modifications is crucial to understand gene regulation. In order to study the most predictive histone modification for active enhancers we created unbiased set of enhancers and used machine learning approach. Our approach revealed an unconventional histone modification H2BK20ac as most efficient marker of active enhancers. H2BK20ac also showed superior coverage of tissue specific active enhancers in complex invivo samples. Adding H2BK20ac to set of conventional histone modifications lead to identification of new chromatin state which could be active enhancers. H2BK20ac tends to occur only at cell-type specific active promoters and showed higher specificity for related disease mutations than H3K27ac and other histone modifications. Using transient state of BV2 microglia cells after lipopolysaccharide based activation, we found that H2BK20ac also marks cell-state specific cis-regulatory elements. Further analysis using inhibition of TGF-beta pathway in BV2 cells and LPS stimulation, revealed differential patterns of H2BK20ac and H3K27ac at genome locations associated with opposite roles response to stmulation. Our study about H2BK20ac hints about a new mechanism of regulation of cell-type specificity and a distinct mode of action of pathways to maintain balance between cell-responses. Chip-seq of H2BK20ac and other histone modifcation was performed in 3 cell types and embryonic mouse forebrain. The sensitivity for active enhancers was compared for different histone modification ChIP-seq.The level of H2BK20ac at promoters and enhancers was assesed for relationship to cell-type specific expression. H2BK20ac signals were also analysed during cell-state transition when microgila are stimulated by LPS
2016-02-25 | E-GEOD-72886 | biostudies-arrayexpress
Project description:By CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation in silico and genetic deletions in vivo revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-06 | GSE138919 | GEO
Project description:By CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation in silico and genetic deletions in vivo revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE140869 | GEO
Project description:By CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation in silico and genetic deletions in vivo revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE140868 | GEO
Project description:By CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation in silico and genetic deletions in vivo revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE140570 | GEO
Project description:CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE139679 | GEO
Project description:CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE138645 | GEO
Project description:CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE136328 | GEO
Project description:CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
2020-03-01 | GSE135394 | GEO