Abstract 2198: ERK5 inhibition potentiates the effects of leukemia cell differentiation inducers by augmenting the function of master transcription factors

2015 ◽  
Author(s):  
Ruifang Zheng ◽  
George Studzinski
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Leukemia Cell ◽  
Differentiation Inducers

scholarly journals EZH2 knockdown upregulates expression of the genes involved in T-ALL cell differentiation

2021 ◽  
Author(s):  
Sahar Safaei ◽  
Behzad Baradaran ◽  
Behzad Mansoori ◽  
Masoumeh Fardi ◽  
Elham Baghbani ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ezh2 Expression

Background: EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), as one of the polycyclic group proteins (PcGs), is an epigenetic regulator that plays a crucial role in the pathophysiology of hematologic malignancies through regulating cell differentiation. Also, it is well known that aberrant expression of specific transcription factors can be involved in the pathogenesis of various cancers. Objective: Herein, we aimed to suppress EZH2 expression in MOLT-4 cells, T-ALL (T cell acute lymphoblastic leukemia) cell line, and evaluate the role of EZH2 on the expression of transcription factors that regulate T cell maturation, differentiation, and apoptosis. Methods: EZH2-siRNA was transfected into MOLT-4 cells, and the expression levels of EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were measured using real-time PCR. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was performed to study the effect of EZH2 knockdown on MOLT-4 cell viability. The apoptosis rate of EZH2-siRNA transfected cells was assessed by flow cytometry. The interaction of mentioned genes was investigated using STRING and GO (gene ontology). Results: Our results have shown that EZH2-siRNA transfection can substantially decrease EZH2 expression in MOLT-4 cells. Besides, EZH2 suppression can upregulate NOTCH1, TCF1, IKZF1, and NFATC1 expression levels. EZH2 knockdown does not affect the viability and apoptosis of MOLT-4 cells. The most remarkable protein-protein interaction of EZH2 has been with NOTCH1. Besides, GO analysis has demonstrated that EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were located within nucleoplasm and can regulate RNA polymerase II-mediated transcription. Conclusion: Our results have shown that MOLT-4 cells harbor increased expression of EZH2 in comparison with normal human T cells. EZH2 knockdown can upregulate the expression of the transcription factors involved in T cell differentiation. Thus, EZH2 can halt the differentiation of immature lymphoblastic T cells.

scholarly journals Maternal endotoxin exposure attenuates allergic airway disease in infant rats

2010 ◽  
Vol 298 (5) ◽  
pp. L670-L677 ◽  
Author(s):  
Lei Cao ◽  
Jinxia Wang ◽  
Yingchun Zhu ◽  
Irene Tseu ◽  
Martin Post
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
T Cell ◽  
Airway Disease ◽  
Positive Control ◽  
Allergic Airway Disease ◽  
T Helper ◽  
T Helper 1 ◽  
Pregnant Rats ◽  
Neonatal Immune System

Prenatal exposures to immunogenic stimuli, such as bacterial LPS, have shown to influence the neonatal immune system and lung function. However, no detailed analysis of the immunomodulatory effects of LPS on postnatal T helper cell differentiation has been performed. Using a rat model, we investigated the effect of prenatal LPS exposure on postnatal T cell differentiation and experimental allergic airway disease. Pregnant rats were injected with LPS on day 20 and 21 (term = 22 days). Some of the offspring were sensitized and challenged with ovalbumin. Positive control animals were placebo exposed to saline instead of LPS, whereas negative controls were sensitized with saline. Expression of T cell-related transcription factors and cytokines was quantified in the lung, and airway hyperresponsiveness was measured. Prenatal LPS exposure induced a T helper 1 (TH1) immune milieu in the offspring of rats [i.e., increased T-bet and TH1 cytokine expression while expression of TH2-associated transcription factors (GATA3 and STAT6) and cytokines was decreased]. Prenatal LPS exposure did not trigger TH17 cell differentiation in the offspring. Furthermore, prenatal LPS exposure reduced ovalbumin-induced (TH2-mediated) airway inflammation, eosinophilia, and airway responsiveness. Thus, in utero exposure to endotoxin promotes a TH1 immune environment, which suppresses the development of allergic airway disease later in life.

scholarly journals Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during T Helper Cell Differentiation

Immunity ◽  
2010 ◽  
Vol 32 (6) ◽  
pp. 840-851 ◽  
Author(s):  
Lai Wei ◽  
Golnaz Vahedi ◽  
Hong-Wei Sun ◽  
Wendy T. Watford ◽  
Hiroaki Takatori ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Epigenetic Modifications ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

Ebf1 controls early cell differentiation in the embryonic striatum

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5285-5294 ◽  
Author(s):  
S. Garel ◽  
F. Marin ◽  
R. Grosschedl ◽  
P. Charnay
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Neuronal Differentiation ◽  
Regulatory Proteins ◽  
Targeted Disruption ◽  
Ventral Telencephalon ◽  
Molecular Identity ◽  
Helix Loop Helix ◽  
The Family ◽  
Mantle Cell

Ebf1/Olf-1 belongs to a small multigene family encoding closely related helix-loop-helix transcription factors, which have been proposed to play a role in neuronal differentiation. Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed. Ebf1 targeted disruption affects postmitotic cells that leave the subventricular zone (SVZ) en route to the mantle: they appear to be unable to downregulate genes normally restricted to the SVZ or to activate some mantle-specific genes. These downstream genes encode a variety of regulatory proteins including transcription factors and proteins involved in retinoid signalling as well as adhesion/guidance molecules. These early defects in the SVZ/mantle transition are followed by an increase in cell death, a dramatic reduction in size of the postnatal striatum and defects in navigation and fasciculation of thalamocortical fibres travelling through the striatum. Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon.

mRNA-activated matrices encoding transcription factors as primers of cell differentiation in tissue engineering

Biomaterials ◽  
2020 ◽  
Vol 247 ◽  
pp. 120016 ◽  
Author(s):  
Adriana M. Ledo ◽  
Ana Senra ◽  
Héctor Rilo-Alvarez ◽  
Erea Borrajo ◽  
Anxo Vidal ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Transcription Factors ◽  
Cell Differentiation
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