Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA338748 | ENA |
REPOSITORIES: ENA
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Project description:Lineage-specific transcription factors regulate DNA methylation dynamics during hematopoietic development
| PRJNA338742 | ENA
Project description:Lineage-specific transcription factors regulate DNA methylation dynamics during hematopoietic development [ChIP-Seq]
| PRJNA338747 | ENA
Project description:DNA methylation is a major epigenetic modification for gene silencing and is dramatically altered spatiotemporally during cellular development. However, the roles of DNA methylation dynamics and regulation in cellular development remain unclear. The present analyses of DNA methylome dynamics during hematopoietic development suggest that DNA demethylation pre-defines the gene expression potential of terminal differentiation-specific genes at the progenitor cell stage and is regulated by lineage-specific transcription factors (TFs). Demethylation of majority of hypo-methylated CpGs in terminally differentiated cells occurs during the progenitor cell stage and is associated with rapid upregulation of terminal differentiation-specific genes. Accordingly, TF overrepresentation analyses indicated that lineage-specific TFs regulate DNA demethylation. The present experiments show that RUNX1 induces site-directed active DNA demethylation by recruiting DNA demethylation enzymes. Collectively, the present data indicate an integrated system of DNA methylation and gene expression during cellular development.
2017-08-10 | GSE85524 | GEO
Project description:DNA methylation is a major epigenetic modification for gene silencing and is dramatically altered spatiotemporally during cellular development. However, the roles of DNA methylation dynamics and regulation in cellular development remain unclear. The present analyses of DNA methylome dynamics during hematopoietic development suggest that DNA demethylation pre-defines the gene expression potential of terminal differentiation-specific genes at the progenitor cell stage and is regulated by lineage-specific transcription factors (TFs). Demethylation of majority of hypo-methylated CpGs in terminally differentiated cells occurs during the progenitor cell stage and is associated with rapid upregulation of terminal differentiation-specific genes. Accordingly, TF overrepresentation analyses indicated that lineage-specific TFs regulate DNA demethylation. The present experiments show that RUNX1 induces site-directed active DNA demethylation by recruiting DNA demethylation enzymes. Collectively, the present data indicate an integrated system of DNA methylation and gene expression during cellular development.
2017-08-10 | GSE85523 | GEO
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBP-beta prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies. Microarray expression data obtained from differentiating murine hematopoietic cells, 3 independent biological replicates (measured twice) from iRUNX1 culture -/+DOX induction
2013-02-11 | E-GEOD-39662 | biostudies-arrayexpress
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBPM-NM-2 prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies. ChIPseq data from transcription factors Runx1, Fli-1, Scl/Tal1 and C/EBPM-NM-2, histone modification H3K9Ac as well as RNA Pol II obtained from differentiating murine hematopoietic cells
2012-10-18 | E-GEOD-40235 | biostudies-arrayexpress
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBP-beta prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies.
2013-02-11 | GSE39662 | GEO
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBPβ prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies.
2012-10-18 | GSE40235 | GEO
Project description:Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage specific behavior of selected factors. In addition to the orchestrated remodeling of the chromatin landscape, we find that the binding of several transcription factors is strongly associated with specific loss of DNA methylation in one germ layer and in many cases a reciprocal gain in the other layers. Taken together, our work shows context-dependent rewiring of transcription factor binding, downstream signaling effectors, and the epigenome during human embryonic stem cell differentiation.
2015-02-19 | GSE61475 | GEO
Project description:Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage specific behavior of selected factors. In addition to the orchestrated remodeling of the chromatin landscape, we find that the binding of several transcription factors is strongly associated with specific loss of DNA methylation in one germ layer and in many cases a reciprocal gain in the other layers. Taken together, our work shows context-dependent rewiring of transcription factor binding, downstream signaling effectors, and the epigenome during human embryonic stem cell differentiation. 200 ChIP-seq experiments profiling 38 transcription factors (TFs) and several chromatin marks in 5 cell types--male human ES cell line HUES64 and directed differentiation of HUES64 towards mesendoderm (dMS, 12 hours), endoderm (dEN, 120 hours), mesoderm (dME, 120 hours), and ectoderm (dEC, 120 hours). In addition, three ES cell lines were derived with shRNA mediated knockdown of GATA4 and differention toward endoderm (dEN_shGATA4) and mesoderm (dME_shGATA4). These cell lines were used for MNChIP-seq of GATA4, SMAD1, and H3K27Ac and for 4 RRBS experiments in GATA4 knockdown and control cell lines.
2015-02-19 | E-GEOD-61475 | biostudies-arrayexpress