Pioneer transcription factor TAL1 modulates chromatin architecture to induce transcriptional reprogramming in erythropoiesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Lixiang Chen
PROVIDER: PXD064033 | iProX | Mon Jun 29 00:00:00 GMT+01:00 2026
REPOSITORIES: iProX
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Project description:Pioneer transcription factors critically regulate chromatin organization and hematopoietic cell lineage commitment. During erythropoiesis, hematopoietic stem cells undergo dynamic transcriptional and chromatin remodeling to differentiate into erythrocytes. Functionally validated pioneer factors capable of orchestrating erythropoiesis through dynamic chromatin remodeling remain limited, leaving their regulatory mechanisms incompletely resolved. Here, we identify T-cell acute lymphocytic leukemia 1(TAL1) as a pioneer factor that remodels chromatin to drive transcriptional reprogramming during erythropoiesis. By recruiting SWI/SNF complex, TAL1 drives erythroid fate specification while suppressing alternative lineages through lineage-restricted chromatin compartment reorganization. As a pioneer factor, TAL1 recruits chromatin remodelers BPTF and KMT2A to establish erythroid-specific genomic architecture. These complexes collectively execute TAL1 directed differentiation programs by transcriptionally activating erythroid regulators while repressing non-erythroid determinants. Our work establishes a generalizable chromatin accessibility-directed pioneer factor screening strategy, we identify TAL1 as a master pioneer factor and resolve its mechanism in driving erythroid commitment through 3D epigenome restructuring.
2026-06-24 | GSE305041 | GEO
Project description:Pioneer transcription factors critically regulate chromatin organization and hematopoietic cell lineage commitment. During erythropoiesis, hematopoietic stem cells undergo dynamic transcriptional and chromatin remodeling to differentiate into erythrocytes. Functionally validated pioneer factors capable of orchestrating erythropoiesis through dynamic chromatin remodeling remain limited, leaving their regulatory mechanisms incompletely resolved. Here, we identify T-cell acute lymphocytic leukemia 1(TAL1) as a pioneer factor that remodels chromatin to drive transcriptional reprogramming during erythropoiesis. By recruiting SWI/SNF complex, TAL1 drives erythroid fate specification while suppressing alternative lineages through lineage-restricted chromatin compartment reorganization. As a pioneer factor, TAL1 recruits chromatin remodelers BPTF and KMT2A to establish erythroid-specific genomic architecture. These complexes collectively execute TAL1 directed differentiation programs by transcriptionally activating erythroid regulators while repressing non-erythroid determinants. Our work establishes a generalizable chromatin accessibility-directed pioneer factor screening strategy, we identify TAL1 as a master pioneer factor and resolve its mechanism in driving erythroid commitment through 3D epigenome restructuring.
2026-06-24 | GSE304991 | GEO
Project description:Pioneer transcription factors critically regulate chromatin organization and hematopoietic cell lineage commitment. During erythropoiesis, hematopoietic stem cells undergo dynamic transcriptional and chromatin remodeling to differentiate into erythrocytes. Functionally validated pioneer factors capable of orchestrating erythropoiesis through dynamic chromatin remodeling remain limited, leaving their regulatory mechanisms incompletely resolved. Here, we identify T-cell acute lymphocytic leukemia 1(TAL1) as a pioneer factor that remodels chromatin to drive transcriptional reprogramming during erythropoiesis. By recruiting SWI/SNF complex, TAL1 drives erythroid fate specification while suppressing alternative lineages through lineage-restricted chromatin compartment reorganization. As a pioneer factor, TAL1 recruits chromatin remodelers BPTF and KMT2A to establish erythroid-specific genomic architecture. These complexes collectively execute TAL1 directed differentiation programs by transcriptionally activating erythroid regulators while repressing non-erythroid determinants. Our work establishes a generalizable chromatin accessibility-directed pioneer factor screening strategy, we identify TAL1 as a master pioneer factor and resolve its mechanism in driving erythroid commitment through 3D epigenome restructuring.
2026-06-24 | GSE304981 | GEO
Project description:Pioneer transcription factors critically regulate chromatin organization and hematopoietic cell lineage commitment. During erythropoiesis, hematopoietic stem cells undergo dynamic transcriptional and chromatin remodeling to differentiate into erythrocytes. Functionally validated pioneer factors capable of orchestrating erythropoiesis through dynamic chromatin remodeling remain limited, leaving their regulatory mechanisms incompletely resolved. Here, we identify T-cell acute lymphocytic leukemia 1(TAL1) as a pioneer factor that remodels chromatin to drive transcriptional reprogramming during erythropoiesis. By recruiting SWI/SNF complex, TAL1 drives erythroid fate specification while suppressing alternative lineages through lineage-restricted chromatin compartment reorganization. As a pioneer factor, TAL1 recruits chromatin remodelers BPTF and KMT2A to establish erythroid-specific genomic architecture. These complexes collectively execute TAL1 directed differentiation programs by transcriptionally activating erythroid regulators while repressing non-erythroid determinants. Our work establishes a generalizable chromatin accessibility-directed pioneer factor screening strategy, we identify TAL1 as a master pioneer factor and resolve its mechanism in driving erythroid commitment through 3D epigenome restructuring.
2026-07-06 | GSE337274 | GEO
Project description:Pioneer transcription factors critically regulate chromatin organization and hematopoietic cell lineage commitment. During erythropoiesis, hematopoietic stem cells undergo dynamic transcriptional and chromatin remodeling to differentiate into erythrocytes. Functionally validated pioneer factors capable of orchestrating erythropoiesis through dynamic chromatin remodeling remain limited, leaving their regulatory mechanisms incompletely resolved. Here, we identify T-cell acute lymphocytic leukemia 1(TAL1) as a pioneer factor that remodels chromatin to drive transcriptional reprogramming during erythropoiesis. By recruiting SWI/SNF complex, TAL1 drives erythroid fate specification while suppressing alternative lineages through lineage-restricted chromatin compartment reorganization. As a pioneer factor, TAL1 recruits chromatin remodelers BPTF and KMT2A to establish erythroid-specific genomic architecture. These complexes collectively execute TAL1 directed differentiation programs by transcriptionally activating erythroid regulators while repressing non-erythroid determinants. Our work establishes a generalizable chromatin accessibility-directed pioneer factor screening strategy, we identify TAL1 as a master pioneer factor and resolve its mechanism in driving erythroid commitment through 3D epigenome restructuring.
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Project description: Not available
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Project description:Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. However, a prolonged sojourn at high altitude results in an increase in EPO levels followed by a decrease, although erythropoiesis remains elevated at a stable level. The role of hypoxia and related EPO adjustments are not fully understood and contributed to the formulation of the theory of neocytolysis. In this study, we aimed to exclusively evaluate the role of oxygen on erythropoiesis comparing in vitro erythroid differentiation performed at atmospheric oxygen, with a lower oxygen concentration (3% O2) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in a different erythroid development, suggesting no retention of high altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at 3% oxygen, displaying a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation to the concept of neocytolysis.
2022-04-06 | PXD031776 | Pride
Project description:To gain insight into hemogen function during human erythropoiesis, RNA-seq was performed in different type of erythroid cells, such as WT and hemogen KD CD34+ cells, WT and hemogen KD HUDEP2 cells, WT and hemogen KO K562 cells. Notably, depletion of hemogen in these human erythroid cells significantly reduced the expression of genes associated with heme and hemoglobin synthesis, such as ALAS2, HMBS, GYPA, EPOR, and HBB, supporting a positive role of hemogen in erythroid maturation. To further explore hemogen function in mouse embryonic erythropoiesis, RNA-seq was performed in WT and hemogen KO E14.5 fetal liver cells and the data indicated hemogen play a consistently positive role in erythroid maturation-related genes as shown in the human cells, suggested hemogen is conserved activator during the mammalian erythropoiesis.
2022-03-21 | GSE184558 | GEO
Project description:Erythropoiesis in mammalian involves chromatin compaction which is initiated in the early stage of terminal differentiation. The proper condensation of chromatin is essential for the subsequent enucleation of erythroblast, but the characteristics of chromatin compaction and chromatin architecture changes in erythropoiesis are poorly understood. Here, we show that the formation of H3K9me3 long-range interactions which mediated heterochromatin three-dimensional rewiring participant in human erythroid chromatin condensation. TADs structure attenuated and boundary strength weakened globally but selectively maintaining in active chromatin region during terminal erythropoiesis. We demonstrate that the erythroid master regulators GATA1 safeguard the active chromatin structure and ensure the appropriate gene expression, under the chromatin condensation of human terminal erythropoiesis
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