Comparative epigenomics of human and mouse erythropoiesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Austrofundulus limnaeus Mus musculus Homo sapiens
PROVIDER: GSE59801 | GEO | 2014/12/01
SECONDARY ACCESSION(S): PRJNA256270
REPOSITORIES: GEO
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Project description:Enhancers of transcription activate transcription via binding of sequence-specific transcription factors to their target sites in chromatin. In this report, we identify GATA1-bound enhancers genome-wide and find a global reorganization of the nucleosomes at these enhancers during differentiation of hematopoietic stem cells (HSCs) to erythrocytes. We show that the catalytic subunit BRG1 of BAF complexes localizes to these enhancers during differentiation and generates a longer nucleosome repeat length surrounding the GATA1 sites by shifting the flanking nucleosomes away. Intriguing, we find that the nucleosome shifting specifically facilitates binding of TAL1 but not GATA1, which subsequently activates transcription of target genes. Human hematopoietic stem cells (referred as CD34+ cells) were differentiated into erythroid lineage expressing the cell surface marker CD36 (referred as CD36+ cells). To study the function of ATP-dependent chromatin remodeling BAF complexes in the establishment of erythroid specific enhancers during differentiation, we mapped the genome-wide binding sites of GATA1 and TAL1, the key transcription regulators of erythroid differentiation, in CD36+ cells, then determined the genomic positions of the catalytic subunit BRG1 of the BAF complexes and the nucleosome landscapes, by ChIP-Seq and Mnase-Seq, respectively, for both HSCs and the differentiated cells. We compared changes in nucleosome landscapes with BRG1 binding at GATA1 and TAL1 binding sites and found that BRG1 binding is correlated with nucleosome shifting away from the binding sites, which is critical for TAL1 binding. To confirm that BRG1 is responsible for the nucleosome shift, we knocked down BRG1 in CD36+ cells and analyzed the nucleosome changes in the knockdown cells. The data indicated that inhibition of BRG1 caused a nucleosome shift towards the GATA1 or TAL1 sites, indicating that BRG1 is indeed responsible for the observed nucleosome shift.
2011-07-01 | E-GEOD-26501 | biostudies-arrayexpress
Project description:The ability to measure epigenetic features, such as histone modifications and occupancy by transcription factors and co-activators, on a genome-wide scale is advancing the accuracy of CRM predictions. While integration of signals from multiple features is expected to improve predictions, the contribution of each feature to prediction accuracy is not known. We began with predictions of 4,915 erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. Inclusion of additional epigenetic features improved the prediction accuracy, with combinations of TAL1, GATA1, EP300, H3K4me1, and H3K27ac giving high accuracy of enhancer prediction (70%-75% success depending on method of clustering) while maintaining good sensitivity and specificity. Motifs that distinguish active from inactive TAL1 OSs implicate IRFs, STATs, and FOX protein families as candidate positive co-factors with TAL1, while REST (NRSF) and HOX family proteins are implicated in inactivity. While signals for evolutionary constraint were weak over the entire TAL1-bound DNA segments regardless of activity in either assay, phylogenetic preservation of a TF-binding site motif was associated with enhancer activity. The contribution of 8 epigenetic features including H3K27ac to identification of enhancers in 24h-induced G1E-ER4 cells.
2015-04-27 | E-GEOD-61349 | biostudies-arrayexpress
Project description:Erythroid development and differentiation from multiprogenitor cells to red blood cells requires precise transcriptional regulation. Key erythroid transcription factors, GATA1 and TAL1, co-operate, along with other proteins, to regulate many aspects of this process. How GATA1 and TAL1 are positionally organized with respect to each other and their cognate DNA binding site across the mouse genome remains unclear. We applied high resolution ChIP-exo to GATA1 and TAL1 to study their positional organization across the mouse genome during GATA1-dependent maturation. Two complementary methods, MultiGPS and peak-pairing, were used to determine high confidence binding locations by ChIP-exo. We identified ~10,000 GATA1 and ~15,000 TAL1 locations, which were essentially confirmed by ChIP-seq. Of these, ~4,000 locations were bound by both GATA1 and TAL1. About three-quarters of these were tightly linked (<40 bp away) to a partial E-box located 7-8 bp upstream of a WGATAA motif. Both TAL1 and GATA1 generated distinct characteristic ChIP-exo peaks around WGATAA motifs, that reflect on their positional arrangement within a complex. We show that TAL1 and GATA1 form a precisely organized complex at a compound motif consisting of a TG 7-8 bp upstream of a WGATAA motif across thousands of genomic locations. Genome wide analysis of GATA1 and TAL1 in G1E and G1E-ER4 cells using ChIP-exo experiments
2015-09-17 | E-GEOD-68964 | biostudies-arrayexpress
Project description:We report the occupancy of GATA1 and TAL1, two erythroid transcription factors, and H3K27ac histone modification in human erythroid precursors.
2017-01-10 | GSE93372 | GEO
Project description:Erythroid development and differentiation from multiprogenitor cells to red blood cells requires precise transcriptional regulation. Key erythroid transcription factors, GATA1 and TAL1, co-operate, along with other proteins, to regulate many aspects of this process. How GATA1 and TAL1 are positionally organized with respect to each other and their cognate DNA binding site across the mouse genome remains unclear. We applied high resolution ChIP-exo to GATA1 and TAL1 to study their positional organization across the mouse genome during GATA1-dependent maturation. Two complementary methods, MultiGPS and peak-pairing, were used to determine high confidence binding locations by ChIP-exo. We identified ~10,000 GATA1 and ~15,000 TAL1 locations, which were essentially confirmed by ChIP-seq. Of these, ~4,000 locations were bound by both GATA1 and TAL1. About three-quarters of these were tightly linked (<40 bp away) to a partial E-box located 7-8 bp upstream of a WGATAA motif. Both TAL1 and GATA1 generated distinct characteristic ChIP-exo peaks around WGATAA motifs, that reflect on their positional arrangement within a complex. We show that TAL1 and GATA1 form a precisely organized complex at a compound motif consisting of a TG 7-8 bp upstream of a WGATAA motif across thousands of genomic locations.
2015-09-17 | GSE68964 | GEO
Project description:The ability to measure epigenetic features, such as histone modifications and occupancy by transcription factors and co-activators, on a genome-wide scale is advancing the accuracy of CRM predictions. While integration of signals from multiple features is expected to improve predictions, the contribution of each feature to prediction accuracy is not known. We began with predictions of 4,915 erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. Inclusion of additional epigenetic features improved the prediction accuracy, with combinations of TAL1, GATA1, EP300, H3K4me1, and H3K27ac giving high accuracy of enhancer prediction (70%-75% success depending on method of clustering) while maintaining good sensitivity and specificity. Motifs that distinguish active from inactive TAL1 OSs implicate IRFs, STATs, and FOX protein families as candidate positive co-factors with TAL1, while REST (NRSF) and HOX family proteins are implicated in inactivity. While signals for evolutionary constraint were weak over the entire TAL1-bound DNA segments regardless of activity in either assay, phylogenetic preservation of a TF-binding site motif was associated with enhancer activity.
2015-04-27 | GSE61349 | GEO
Project description:Mammals express thousands of long noncoding (lnc) RNAs, a few of which are shown to function in tissue development. However, the entire repertoire of lncRNAs and the extent to which they regulate biological processes in different tissues and species are not defined. Indeed, most lncRNAs are not conserved between species, raising questions about function. We used RNA-Seq to identify lncRNAs in primary murine fetal liver erythroblasts expressing the lineage marker TER119, megakaryocytes (CD41+) cultured from embryonic day (E) 14.5 murine fetal liver and megakaryocyte erythroid progenitors (MEPs) isolated from mouse bone marrow. We identified 683 and 594 polyadenylated lncRNAs expressed in red blood cell (erythroid) precursors of mice and humans, respectively. More than one half of erythroid lncRNAs are un-annotated, emphasizing the opportunity for new discovery through studies of specialized cell types. We analyzed the expression of these identified lncRNAs in several hematopoietic compartments using a custom microarray to identify erythroid-specific lncRNAs that were robustly expressed in both fetal liver and adult erythroid cells as targets for knockdown. Over 90% of fetal liver erythroid lncRNAs detected using RNA-seq were expressed in adult erythroblasts measured on the microarray. Analysis of the murine erythroid lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by the key erythroid transcription factors GATA1 and SCL/TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatically greater species-specificity than coding genes. We investigated potential functions of 21 relatively abundant erythroid-specific murine lncRNAs (both conserved and non-conserved) by RNA interference in primary mouse erythroid precursors, and identified 7 whose knockdown inhibited features of terminal erythroid maturation including cell size reduction and enucleation. Strikingly, at least 6 of the 7 lncRNAs have no detectable expression in human erythroblasts, demonstrating that lack of conservation between mammalian species does not predict lack of function. These results reflect marked evolutionary differences between protein-coding genes and lncRNAs and indicate that the latter exert tissue- and species-specific roles in development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2014-02-20 | GSE51892 | GEO
Project description:Mammals express thousands of long noncoding (lnc) RNAs, a few of which are shown to function in tissue development. However, the entire repertoire of lncRNAs and the extent to which they regulate biological processes in different tissues and species are not defined. Indeed, most lncRNAs are not conserved between species, raising questions about function. We used RNA-Seq to identify lncRNAs in primary murine fetal liver erythroblasts expressing the lineage marker TER119, megakaryocytes (CD41+) cultured from embryonic day (E) 14.5 murine fetal liver and megakaryocyte erythroid progenitors (MEPs) isolated from mouse bone marrow. Strand-specific, paired-end, deep sequencing was performed on polyA+ mRNA from biological replicates of each sample. We assembled the transcriptomes using the Cufflinks package and generated a high-confidence transcriptome of 13,131 genes expressed in the three cell types. We identified 683 and 594 polyadenylated lncRNAs expressed in red blood cell (erythroid) precursors of mice and humans, respectively. More than one half of erythroid lncRNAs are un-annotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the murine erythroid lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by the key erythroid transcription factors GATA1 and SCL/TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatically greater species-specificity than coding genes. We investigated potential functions of 21 relatively abundant erythroid-specific murine lncRNAs (both conserved and non-conserved) by RNA interference in primary mouse erythroid precursors, and identified 7 whose knockdown inhibited features of terminal erythroid maturation including cell size reduction and enucleation. Strikingly, at least 6 of the 7 lncRNAs have no detectable expression in human erythroblasts, demonstrating that lack of conservation between mammalian species does not predict lack of function. These results reflect marked evolutionary differences between protein-coding genes and lncRNAs and indicate that the latter exert tissue- and species-specific roles in development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2014-02-20 | GSE51667 | GEO
Project description:Mammals express thousands of long noncoding (lnc) RNAs, a few of which are shown to function in tissue development. However, the entire repertoire of lncRNAs and the extent to which they regulate biological processes in different tissues and species are not defined. Indeed, most lncRNAs are not conserved between species, raising questions about function. We used RNA-Seq to identify lncRNAs in primary murine fetal liver erythroblasts expressing the lineage marker TER119, megakaryocytes (CD41+) cultured from embryonic day (E) 14.5 murine fetal liver and megakaryocyte erythroid progenitors (MEPs) isolated from mouse bone marrow. We identified 683 and 594 polyadenylated lncRNAs expressed in red blood cell (erythroid) precursors of mice and humans, respectively. More than one half of erythroid lncRNAs are un-annotated, emphasizing the opportunity for new discovery through studies of specialized cell types. We analyzed the expression of these identified lncRNAs in several hematopoietic compartments using a custom microarray to identify erythroid-specific lncRNAs that were robustly expressed in both fetal liver and adult erythroid cells as targets for knockdown. Over 90% of fetal liver erythroid lncRNAs detected using RNA-seq were expressed in adult erythroblasts measured on the microarray. Analysis of the murine erythroid lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by the key erythroid transcription factors GATA1 and SCL/TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatically greater species-specificity than coding genes. We investigated potential functions of 21 relatively abundant erythroid-specific murine lncRNAs (both conserved and non-conserved) by RNA interference in primary mouse erythroid precursors, and identified 7 whose knockdown inhibited features of terminal erythroid maturation including cell size reduction and enucleation. Strikingly, at least 6 of the 7 lncRNAs have no detectable expression in human erythroblasts, demonstrating that lack of conservation between mammalian species does not predict lack of function. These results reflect marked evolutionary differences between protein-coding genes and lncRNAs and indicate that the latter exert tissue- and species-specific roles in development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf A custom Agilent microarray was designed to interrogate expression levels of long noncoding RNAs identified using RNA-seq in several different hematopoietic progenitor and differentiated cell populations. LncRNA gene definitions and RNA-seq data used to identify long noncoding RNAs are deposited in GEO with the accession numbers GSE51667 and GSE40522 respectively. The Agilent eArray platform was used to customize the SurePrint G3 Mouse GE 8x60K microarray to add 3 custom-designed probes (60nt length) each against several categories of genes, namely pseudogene, genes with small RNA overlap, low stringency lncRNAs and high stringency lncRNAs . We interrogated 7 types of hematopoietic cells, HSC, CMP, MEP, GMP, early and late erythroblasts and granulocytes. Expression measurements were determined at least in duplicate for all samples and in triplicate for most samples.
2014-02-20 | E-GEOD-51892 | biostudies-arrayexpress
Project description:We used mouse ENCODE data along with complementary data from other laboratories to study the dynamics of occupancy and the role in gene regulation of the transcription factor TAL1, a critical regulator of hematopoiesis, at multiple stages of hematopoietic differentiation. We combined ChIP-seq and RNA-seq data in six mouse cell types representing a progression from multilineage precursors to differentiated erythroblasts and megakaryocytes. We found that sites of occupancy shift dramatically during commitment to the erythroid lineage, vary further during terminal maturation, and are strongly associated with changes in gene expression. In multilineage progenitors, the likely target genes are enriched for hematopoietic growth and functions associated with the mature cells of specific daughter lineages (such as megakaryocytes). In contrast, target genes in erythroblasts are specifically enriched for red cell functions. Furthermore, shifts in TAL1 occupancy during erythroid differentiation are associated with gene repression (dissociation) and induction (co-occupancy with GATA1). Based on both enrichment for transcription factor binding site motifs and co-occupancy determined by ChIP-seq, recruitment by GATA transcription factors appears to be a stronger determinant of TAL1 binding to chromatin than the canonical E-box binding site motif. Studies of additional proteins lead to the model that TAL1 regulates expression after being directed to a distinct subset of genomic binding sites in each cell type via its association with different complexes containing master regulators such as GATA2, ERG, and RUNX1 in multilineage cells and the lineage-specific master regulator GATA1 in erythroblasts. Combined ChIP-seq and RNA-seq data in six mouse cell types representing a progression from multilineage precursors to differentiated erythroblasts and megakaryocytes.
2014-11-14 | E-GEOD-51338 | biostudies-arrayexpress