A Positive Regulatory Feedback Loop Between EKLF/ KLF1 and TAL1/SCL Sustaining the Erythropoiesis
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PROVIDER: PRJNA719026 | ENA |
REPOSITORIES: ENA
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Project description:KLF1 (EKLF) regulates a diverse suite of genes to direct erythroid cell differentiation from bi-potent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as β-globin, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of α and β-globin protein chains, heme biosynthesis, co-ordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 co-operation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.
2010-04-08 | GSE20478 | GEO
Project description:KLF1 (EKLF) regulates a diverse suite of genes to direct erythroid cell differentiation from bi-potent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as β-globin, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of α and β-globin protein chains, heme biosynthesis, co-ordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 co-operation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment. Examination of KLF1 occupancy in primary erythroid cells. KLF1-ChIP and input samples were run on AB SOLiD Systems 2.0 and 3.0. The genomic alignment files (*sorted.txt) and peak file (*bed) contain the combined System 2.0 and 3.0 data.
2010-04-08 | E-GEOD-20478 | biostudies-arrayexpress
Project description:The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf-/-) mouse embryos, we have identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with molecular/ cellular analysis of mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tall gene promoter in combination with in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates Tall gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors that sustains the mammalian erythropoiesis.
2022-03-31 | GSE171201 | GEO
Project description:The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf-/-) mouse embryos, we have identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with molecular/ cellular analysis of mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tall gene promoter in combination with in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates Tall gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors that sustains the mammalian erythropoiesis.
2022-03-31 | GSE171200 | GEO
Project description:EKLF/Klf1 is a Zinc-finger transcription activator essential for erythroid lineage commitment and terminal differentiation. Using ChIP-Seq, we investigate EKLF DNA binding and transcription activation mechanisms during mouse embryonic erythropoiesis. Our study focuses on global EKLF binding dynamics during embryonic erythropoiesis in primary WT and Nan/+ mouse fetal liver, and its correlation with chromatin accessibility, CBP occupancy, histone acetylation, and finally its effect on RNA Polymerase II pausing and elongation. Our goal is to elucidate the mechanisms of transcription activation by EKLF/Klf1 during embryonic erythropoiesis in vivo and in the context of RNA pol II pause-release control. Additionally, we aim to understand the unusually severe effects of conservative E to D change in Nan-EKLF and the molecular mechanisms leading to dominant anemia through global gene dysregulation.
2023-01-18 | GSE210779 | GEO
Project description:Klf1 (formerly known as Eklf) regulates the development of erythroid cells from bi-potent progenitor cells via the transcriptional activation of a diverse set of genes. Mice lacking Klf1 die in utero prior to E15 from severe anemia due to the inadequate expression of genes controlling hemoglobin production, cell membrane and cytoskeletal integrity, and the cell cycle and proliferation. We have recently described the full repertoire of Klf1 binding sites in vivo by performing Klf1 ChIP-seq in primary erythroid tissue (E14.5 fetal liver). Here we describe the Klf1-dependent erythroid transcriptome by comparing mRNA-seq from Klf1+/+ and Klf1-/- erythroid tissue. This has revealed novel target genes not previously obtainable by traditional microarray technology and provided novel insights into the function of Klf1 as a transcriptional activator such as interactions with Gata1, Scl/Tal1 and p300. We also describe a set of erythroid specific promoters not previously identified that drive high level expression of otherwise ubiquitously expressed genes in erythroid cells. Additionally, our study has identified for the first time two novel lnc-RNAs that are dynamically expressed during erythroid differentiation as well as a role for Klf1 in directing apoptotic gene expression to drive the terminal stages of erythroid maturation. Examination of mRNA expression in 3 Klf1-/- and 3 Klf1+/+ fetal livers This submission represents mRNA-Seq component of study.
2012-04-01 | E-GEOD-33979 | biostudies-arrayexpress
Project description:ChIP-Seq experiments using an Scl/TAL1 antibody were carried out in primary erythroid cells cultured from two individuals of Caucasian origin. ChIP-Seq libraries were prepared from two biological replicates for each individual. ChIP DNA was processed for Illumina High-throughput sequencing according to Illumina protocol. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA from each experiments, we generated a high-resolution map of Scl/TAL1 genomic targets in human erythroid cells. We find that WGATAR and the combinatorial CTG(n9)GATA are the most significant motifs responsible for the chromatin occupancy by Scl/TAL1. In addition, other motifs are also significantly enriched at the Scl/TAL1 targets. Amongst these were binding sites for known TFs (Sp/XKLF, RUNX1, NFE2). We next investigated how many of these targets varied between these two individuals. We find that 0.8% of Scl/TAL1 binding regions differ significantly between the two individuals.
2014-11-08 | GSE42390 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-31 | GSE171289 | GEO
Project description:Klf1 (formerly known as Eklf) regulates the development of erythroid cells from bi-potent progenitor cells via the transcriptional activation of a diverse set of genes. Mice lacking Klf1 die in utero prior to E15 from severe anemia due to the inadequate expression of genes controlling hemoglobin production, cell membrane and cytoskeletal integrity, and the cell cycle and proliferation. We have recently described the full repertoire of Klf1 binding sites in vivo by performing Klf1 ChIP-seq in primary erythroid tissue (E14.5 fetal liver). Here we describe the Klf1-dependent erythroid transcriptome by comparing mRNA-seq from Klf1+/+ and Klf1-/- erythroid tissue. This has revealed novel target genes not previously obtainable by traditional microarray technology and provided novel insights into the function of Klf1 as a transcriptional activator such as interactions with Gata1, Scl/Tal1 and p300. We also describe a set of erythroid specific promoters not previously identified that drive high level expression of otherwise ubiquitously expressed genes in erythroid cells. Additionally, our study has identified for the first time two novel lnc-RNAs that are dynamically expressed during erythroid differentiation as well as a role for Klf1 in directing apoptotic gene expression to drive the terminal stages of erythroid maturation.
2012-04-01 | GSE33979 | GEO
Project description:Erythroid Krüppel Like Factor (EKLF/ KLF1) is a C2H2 zinc finger transcription factor that plays a critical role in all aspects of erythropoiesis. Mutations in KLF1 lead to diverse phenotypes ranging from mild to severe anemias. Patients with a heterozygous E325K mutation (CDA type IV) exhibit impaired erythroid terminal differentiation and increased presence of binucleate erythroblasts. We previously showed that KLF1 is necessary for cell cycle exit and enucleation in mouse primary cells. In the current study we discovered that genes involved in cell motility, cell division, and mitotic pathways are all directly regulated by KLF1. Klf1-/- cells exhibit increased numbers of binucleated erythroblasts and DNA bridges, and differentiating Klf1-/- erythroblasts display an increased percentage of cytokinesis failure events and defective microtubule bundling. Klf1-/- erythroblasts produce frequent aberrant F-actin-rich membrane protrusions and anucleate cell fragments. Human CDA type IV cells exhibit similar patterns of dysregulation of cytokinesis and cell motility genes. Collectively, we show that KLF1 is necessary for maintaining the integrity of erythroid cell divisions by direct regulation of genes involved in cytokinesis and motility pathways during terminal erythroid differentiation.
2026-07-20 | GSE338783 | GEO