Hematopoiesis and cell growth are differentially regulated by TAL1 isoforms [ChIP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA894966 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22064273.fastq.gz | Fastqsanger.gz | |||
| SRR22064274.fastq.gz | Fastqsanger.gz | |||
| SRR22064275.fastq.gz | Fastqsanger.gz | |||
| SRR22064276.fastq.gz | Fastqsanger.gz | |||
| SRR22064277.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Hematopoiesis and cell growth are differentially regulated by TAL1 isoforms
| PRJNA887369 | ENA
Project description:T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is the most common cause of T-ALL. Here we studied the two protein isoforms of TAL1, short and long, that are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5’ UTR with differential regulation of translation. In addition, the enhancers regulate TAL1 exon 3 alternative splicing by altering the chromatin at its location. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and function as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, expressing both isoforms in mice bone marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone reduced survival capability of hematopoietic stem cells. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the AML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoform’s ratio could be a preferred therapeutic approach.
2023-04-30 | GSE214833 | GEO
Project description:T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is the most common cause of T-ALL. Here we studied the two protein isoforms of TAL1, short and long, that are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5’ UTR with differential regulation of translation. In addition, the enhancers regulate TAL1 exon 3 alternative splicing by altering the chromatin at its location. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and function as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, expressing both isoforms in mice bone marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone reduced survival capability of hematopoietic stem cells. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the AML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoform’s ratio could be a preferred therapeutic approach.
2023-04-30 | GSE216684 | GEO
Project description:A network of gene regulatory factors such as transcription factors and microRNAs establish and maintain the gene expression pattern during hematopoiesis. In this network transcription factors regulate each other and are involved in regulatory loops with microRNAs.The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes for six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.
2021-09-09 | PXD018052 | Pride
Project description:miRNA profiling of Jurkat T-ALL cells after knockdown with two control shRNAs and two shRNAs targeting TAL1 to identify miRNAs that are regulated by TAL1
2013-06-15 | GSE46957 | GEO
Project description:miRNA profiling of Jurkat T-ALL cells after knockdown with two control shRNAs and two shRNAs targeting TAL1 to identify miRNAs that are regulated by TAL1 miRNA profiling using Exiqon arrays 48hrs after transduction of Jurkat cells with two control shRNAs (pLKO1-GFP and pLKO1-LUCIFERASE) vs two shRNAs targeting TAL1 (pLKO1-shRNA1 and pLKO1-shRNA2). Biological duplicates per shRNA. One replicate per array.Total of 8 arrays.
2013-06-15 | E-GEOD-46957 | biostudies-arrayexpress
Project description:miR-222 isoforms are differentially regulated by type-I interferon
| PRJEB22632 | ENA
Project description:The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1.
| PRJNA489288 | ENA
Project description:Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury-positive multipotent cells in the posterior-proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite their being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR/Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers.
2019-02-20 | GSE119467 | GEO
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