scholarly journals The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5523-5531 ◽  
Author(s):  
I. Pata ◽  
M. Studer ◽  
J.H. van Doorninck ◽  
J. Briscoe ◽  
S. Kuuse ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Motor Neurons ◽  
Ectopic Expression ◽  
Downstream Effector ◽  
Gata3 Expression ◽  
Efferent Neurons ◽  
Facial Branchiomotor Neurons ◽  
Deficient Mice ◽  
Rhombomere 4

In this paper, we show that the transcription factor GATA3 is dynamically expressed during hindbrain development. Function of GATA3 in ventral rhombomere (r) 4 is dependent on functional GATA2, which in turn is under the control of Hoxb1. In particular, the absence of Hoxb1 results in the loss of GATA2 expression in r4 and the absence of GATA2 results in the loss of GATA3 expression. The lack of GATA3 expression in r4 inhibits the projection of contralateral vestibuloacoustic efferent neurons and the migration of facial branchiomotor neurons similar to Hoxb1-deficient mice. Ubiquitous expression of Hoxb1 in the hindbrain induces ectopic expression of GATA2 and GATA3 in ventral r2 and r3. These findings demonstrate that GATA2 and GATA3 lie downstream of Hoxb1 and provide the first example of Hox pathway transcription factors within a defined population of vertebrate motor neurons.

Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4406-4414 ◽  
Author(s):  
Wei Xu ◽  
Barbara L. Kee
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
T Lymphocyte ◽  
Cell Expansion ◽  
Target Gene ◽  
Ectopic Expression ◽  
Growth Arrest ◽  
T Cell Lymphomas ◽  
Gata3 Expression

AbstractThe E2A transcription factors are required for normal T lymphopoiesis and to prevent T-lymphocyte progenitor transformation. Ectopic expression of E2A proteins in E2A-deficient lymphomas results in growth arrest and apoptosis, indicating that these cells remain responsive to the targets of E2A. Here we identify the transcriptional repressor growth factor independent 1B (Gfi1b) as a target of E2A that promotes growth arrest and apoptosis in lymphomas. Gfi1b expression in primary T-lymphocyte progenitors is dependent on E2A and excess Gfi1b prevents the outgrowth of T lymphocyte progenitors in vitro. Gfi1b represses expression of Gata3, a transcription factor whose appropriate regulation is required for survival of lymphomas and T-lymphocyte progenitors. We also show that ectopic expression of Gata3 in lymphomas promotes expression of Gfi1b, indicating that these proteins may function in an autoregulatory loop that maintains appropriate levels of Gata3. Therefore, we propose that E2A proteins prevent lymphoma cell expansion, at least in part through regulation of Gfi1b and modulation of Gata3 expression.

The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5191-5201 ◽  
Author(s):  
V. Dubreuil ◽  
M. Hirsch ◽  
A. Pattyn ◽  
J. Brunet ◽  
C. Goridis
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Fate ◽  
Motor Neurons ◽  
Ventricular Zone ◽  
Ectopic Expression ◽  
Neuronal Cell ◽  
Cell Cycle Exit ◽  
Neuronal Precursors ◽  
Regulation Of Cell Cycle

In the vertebrate neural tube, cell cycle exit of neuronal progenitors is accompanied by the expression of transcription factors that define their generic and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly understood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic. In the absence of Phox2b, post-mitotic neuronal precursors are not generated in proper numbers. Conversely, forced expression of Phox2b in the embryonic chick spinal cord drives ventricular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation characterised by expression of Islet1 and of the cholinergic transmitter phenotype, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons. These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.

scholarly journals ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism

2015 ◽  
Vol 29 (10) ◽  
pp. 1510-1521 ◽  
Author(s):  
F. Castinetti ◽  
M. L. Brinkmeier ◽  
A. H. Mortensen ◽  
K. R. Vella ◽  
P. Gergics ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Motor Neurons ◽  
Heart Defects ◽  
Normal Serum ◽  
Early Embryogenesis ◽  
Pituitary Cells ◽  
Specific Expression ◽  
Obvious Effect ◽  
Deficient Mice ◽  
Serum Tsh

Abstract ISLET1 is a homeodomain transcription factor necessary for development of the pituitary, retina, motor neurons, heart, and pancreas. Isl1-deficient mice (Isl1−/−) die early during embryogenesis at embryonic day 10.5 due to heart defects, and at that time, they have an undersized pituitary primordium. ISL1 is expressed in differentiating pituitary cells in early embryogenesis. Here, we report the cell-specific expression of ISL1 and assessment of its role in gonadotropes and thyrotropes. Isl1 expression is elevated in pituitaries of Cga−/− mice, a model of hypothyroidism with thyrotrope hypertrophy and hyperplasia. Thyrotrope-specific disruption of Isl1 with Tshb-cre is permissive for normal serum TSH, but T4 levels are decreased, suggesting decreased thyrotrope function. Inducing hypothyroidism in normal mice causes a reduction in T4 levels and dramatically elevated TSH response, but mice with thyrotrope-specific disruption of Isl1 have a blunted TSH response. In contrast, deletion of Isl1 in gonadotropes with an Lhb-cre transgene has no obvious effect on gonadotrope function or fertility. These results show that ISL1 is necessary for maximal thyrotrope response to hypothyroidism, in addition to its role in development of Rathke's pouch.

scholarly journals Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration

2020 ◽  
Author(s):  
Yuyan Cheng ◽  
Yuqin Yin ◽  
Alice Zhang ◽  
Alexander Bernstein ◽  
Riki Kawaguchi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Motor Neurons ◽  
Ganglion Cells ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Integrative Genomics ◽  
Cortical Motor ◽  
Cord Injury ◽  
Cell Type Specific

Abstract The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we used a system-genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST showed improved regeneration of the corticospinal tract and optic nerve, accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a novel role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the power of a systems biology approach involving integrative genomics and bio-informatics to predict key regulators of CNS repair.

scholarly journals Ectopic Overproduction of a Sporulation-Specific Transcription Factor Induces Assembly of Prespore-Like Membranous Compartments in Vegetative Cells of Fission Yeast

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 1195-1199 ◽  
Author(s):  
Yukiko Nakase ◽  
Aiko Hirata ◽  
Chikashi Shimoda ◽  
Taro Nakamura
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Fission Yeast ◽  
Nuclear Division ◽  
Ectopic Expression ◽  
Vegetative Cells ◽  
Common Features ◽  
Specific Transcription Factor

Mei4 is a key sporulation-specific transcription factor in fission yeast. Ectopic expression of Mei4 in vegetative cells caused formation of nucleated membranous compartments, which shared common features with normal forespore membranes, thereby perturbing nuclear division. These results suggest why expression of development-specific transcription factors must be strictly controlled.

scholarly journals Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration

2020 ◽  
Author(s):  
Yuyan Cheng ◽  
Yuqin Yin ◽  
Alice Zhang ◽  
Alexander M. Bernstein ◽  
Riki Kawaguchi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Motor Neurons ◽  
Ganglion Cells ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Integrative Genomics ◽  
Cortical Motor ◽  
Cord Injury ◽  
Cell Type Specific

SUMMARYThe inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we used a system-genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST showed improved regeneration of the corticospinal tract and optic nerve, accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a novel role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the power of a systems biology approach involving integrative genomics and bio-informatics to predict key regulators of CNS repair.

scholarly journals LncRNA lncLy6C induced by microbiota metabolite butyrate promotes differentiation of Ly6Chigh to Ly6Cint/neg macrophages through lncLy6C/C/EBPβ/Nr4A1 axis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yunhuan Gao ◽  
Jiang Zhou ◽  
Houbao Qi ◽  
Jianmei Wei ◽  
Yazheng Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Gut Microbiota ◽  
Promoter Region ◽  
Inflammatory Monocytes ◽  
Pathological Conditions ◽  
Lysine Methyltransferases ◽  
Factor C ◽  
Two Populations ◽  
Deficient Mice

AbstractMacrophages are mainly divided into two populations, which play a different role in physiological and pathological conditions. The differentiation of these cells may be regulated by transcription factors. However, it is unclear how to modulate these transcription factors to affect differentiation of these cells. Here, we found that lncLy6C, a novel ultraconserved lncRNA, promotes differentiation of Ly6Chigh inflammatory monocytes into Ly6Clow/neg resident macrophages. We demonstrate that gut microbiota metabolites butyrate upregulates the expression of lncLy6C. LncLy6C deficient mice had markedly increased Ly6Chigh pro-inflammatory monocytes and reduced Ly6Cneg resident macrophages. LncLy6C not only bound with transcription factor C/EBPβ but also bound with multiple lysine methyltransferases of H3K4me3 to specifically promote the enrichment of C/EBPβ and H3K4me3 marks on the promoter region of Nr4A1, which can promote Ly6Chigh into Ly6Cneg macrophages. As a result, lncLy6C causes the upregulation of Nr4A1 to promote Ly6Chigh inflammatory monocytes to differentiate into Ly6Cint/neg resident macrophages.

scholarly journals Low levels of Grainy head isoforms regulate Drosophila midgut intestinal stem cell differentiation

2020 ◽  
Author(s):  
Nicole Dominado ◽  
Franca Casagranda ◽  
Nicole A. Siddall ◽  
Helen E. Abud ◽  
Gary R. Hime
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Transcription Factors ◽  
Ectopic Expression ◽  
Stem Cell Differentiation ◽  
Intestinal Stem Cells ◽  
Stem Cell Maintenance ◽  
Low Levels ◽  
High Level

AbstractRegeneration of the Drosophila midgut epithelium depends upon differential expression of transcription factors in intestinal stem cells and their progeny. The grainy head locus produces multiple splice forms that result in production of two classes of transcription factor, designated Grh.O and Grh.N. grainy head is expressed at very low levels in the midgut and yet Grh.O is required for maintenance of intestinal stem cells and exhibits a second function regulating enteroblast differentiation in conjunction with miR-8 and Zfh-1. Grh.O expression must be tightly regulated as high level ectopic expression in enteroblasts results in cells with confused identity and promotes excess proliferation in the epithelium. Expression of Grh.N in intestinal stem cells promotes differentiation to enterocytes. Thus midgut regeneration is not only dependent upon signalling pathways that regulate transcription factor expression, but also upon regulated mRNA splicing of these genes. This study also indicates that networks of transcription factors are acting at very low levels to regulate stem cell maintenance and differentiation.

Mechanisms of aberrant GATA3 expression in classical Hodgkin lymphoma and its consequences for the cytokine profile of Hodgkin and Reed/Sternberg cells

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4202-4211 ◽  
Author(s):  
Jens Stanelle ◽  
Claudia Döring ◽  
Martin-Leo Hansmann ◽  
Ralf Küppers
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Hodgkin Lymphoma ◽  
Constitutive Activity ◽  
Classical Hodgkin Lymphoma ◽  
Notch 1 ◽  
Aberrant Expression ◽  
Gata3 Expression ◽  
And Function ◽  
Unique Composition

Abstract The transcription factor network in Hodgkin lymphoma (HL) represents a unique composition of proteins found in no other hematopoietic cell. Among these factors, an aberrant expression of the T-cell transcription factor GATA3 is observed in B cell–derived Hodgkin and Reed/Sternberg (HRS) tumor cells. Herein, we elucidate the regulation and function of this factor in HL. We demonstrate binding of NFκB and Notch-1, 2 factors with deregulated activity in HL to GATA3 promoter elements. Interference with NFκB and Notch-1 activity led to decreased GATA3 expression, indicating a dependency of deregulated GATA3 expression on these transcription factors. Down-regulation of GATA3 in HL cell lines demonstrated its role in the regulation of IL-5, IL-13, STAT4, and other genes. A correlation between GATA3 and IL-13 expression was confirmed for HRS cells in HL tissues. Thus, GATA3 shapes the cytokine expression and signaling that is typical of HL. Conclusively, aberrant GATA3 expression in HRS cells is stimulated by the deregulated constitutive activity of NFκB and Notch-1, indicating a complex network of deregulated transcription factors in these cells. GATA3 activity significantly contributes to the typical cytokine secretion of and signaling in HRS cells, which presumably plays an essential role in HL pathogenesis.

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