Negative regulation of lymphoid specification by the transcription factor Tal1
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PROVIDER: PRJNA521146 | ENA |
REPOSITORIES: ENA
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Project description:Negative regulation of lymphoid specification by the transcription factor TAL1
| PRJNA521778 | ENA
Project description:Lymphoid primed multipotent progenitors are a subset of MPPs that are undergoing specification to the lymphoid and myeloid cell fates. The transcription factors Lyl1 and E2A are both essential for the development LMPPs and can form a heterodimeric complex. We examined the consequences of E2A- or Lyl1-deficiency on development of LMPPs and on their gene expression program in comparison with wild-type LMPPs
2019-02-12 | GSE126402 | GEO
Project description:Lymphoid primed multipotent progenitors are a subset of MPPs that are undergoing specification to the lymphoid and myeloid cell fates. The transcription factors Lyl1 and E2A are both essential for the development LMPPs and can form a heterodimeric complex. We examined the consequences of E2A- or Lyl1-deficiency on development of LMPPs and on their gene expression program in comparison with wild-type LMPPs We used microarray data to examine the differences in gene expression between control, E2A-/- and Lyl1-/- CD138+ LSK cells.
2019-02-07 | GSE126148 | GEO
Project description:The ubiquitin ligase Huwe1 regulates stem cell quiescence, maintenance and lymphoid specification by controlling the expression of N-Myc.
2016-08-18 | GSE85488 | 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:Collombet2016 - Lymphoid and myeloid cell
specification and transdifferentiation
This model is described in the article:
Logical modeling of lymphoid
and myeloid cell specification and transdifferentiation
Samuel Collombet, Chris van Oevelen,
Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di
Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis
Thieffry
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Blood cells are derived from a common set of hematopoietic
stem cells, which differentiate into more specific progenitors
of the myeloid and lymphoid lineages, ultimately leading to
differentiated cells. This developmental process is controlled
by a complex regulatory network involving cytokines and their
receptors, transcription factors, and chromatin remodelers.
Using public data and data from our own molecular genetic
experiments (quantitative PCR, Western blot, EMSA) or
genome-wide assays (RNA-sequencing, ChIP-sequencing), we have
assembled a comprehensive regulatory network encompassing the
main transcription factors and signaling components involved in
myeloid and lymphoid development. Focusing on B-cell and
macrophage development, we defined a qualitative dynamical
model recapitulating cytokine-induced differentiation of common
progenitors, the effect of various reported gene knockdowns,
and the reprogramming of pre-B cells into macrophages induced
by the ectopic expression of specific transcription factors.
The resulting network model can be used as a template for the
integration of new hematopoietic differentiation and
transdifferentiation data to foster our understanding of
lymphoid/myeloid cell-fate decisions.
This model is hosted on
BioModels Database
and identified by:
MODEL1610240000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-08 | MODEL1610240000 | BioModels
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:We used microarray profiling in erythroid cells to uncover TAL1 dependent genes in a hematopoietic differentiation context. Differentiated ex vivo hematopoietic multipotential progenitors isolated from adult peripheral blood. The knockdown of TAL1 (KD) was induced in pro-erythroblasts (Days 8 and 9 of differentiation) using lentivirus-delivered shRNA. A scramble (scr) shRNA sequence was used as a negative control.
2010-12-14 | E-GEOD-20545 | biostudies-arrayexpress
Project description:TAL1/SCL is a master regulator of hematopoiesis whose expression promotes opposite outcomes depending on the cell type - differentiation in the erythroid lineage or oncogenesis in the T-cell lineage. Here we used a combination of ChIP-sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukemic T-cells. Analysis of the genome-wide binding properties of TAL1 in these two hematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. Our study shows limited overlap in the TAL1 binding profile between the two cell types with an unexpected preference for ETS and RUNX motifs adjacent to E-boxes in the T-cell lineage. Furthermore we show that TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required to target TAL1 to genes that modulate T-cell differentiation. Thus, our findings highlight a critical role of the cellular environment in modulating transcription factor binding, and provide insight into the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in the T-cell lineage.
2010-10-30 | GSE25000 | 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