scholarly journals Retinoic acid and the transcription factor MafB act together and differentially to regulate aggrecan and matrix metalloproteinase gene expression in neonatal chondrocytes

2012 ◽  
Vol 114 (2) ◽  
pp. 471-479 ◽  
Author(s):  
Yao Zhang ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Matrix Metalloproteinase

MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4197-4197
Author(s):  
Jeannet Nigten ◽  
Ruth Knops ◽  
Gorica Nikoloski ◽  
Theo M. de Witte ◽  
Bert A. van der Reijden ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Cell Differentiation ◽  
Fusion Protein ◽  
Acute Promyelocytic Leukemia ◽  
Mirna Expression ◽  
Promyelocytic Leukemia ◽  
Mirna Genes ◽  
Before And After

Abstract The discovery of the microRNA (miRNA) molecules has led to new insights into the regulation of gene expression. They are able to bind specific mRNA sequences, and due to inhibition of translation or mRNA degradation, miRNAs cause downregulation of their target genes. To date, several hundreds of unique human miRNAs have been described. So far, for only few of them the target mRNAs have been experimentally confirmed. MiRNAs have been linked to several important biological processes as early stage development, cell growth, cell differentiation and apoptosis. In addition, impaired miRNA expression has been implicated in tumorigenesis. Leukemia is often associated with mutated transcription factors and, as a consequence, deregulated gene expression and impaired proliferation and differentiation. Acute Promyelocytic Leukemia (APL), is characterised by the expression of the mutated transcription factor PML-RARα, which may interfere with the normal function of the retinoic acid receptor α (RARα), a nuclear hormone receptor that acts as a ligand-dependent transcription factor. APL is uniquely sensitive to treatment with the RARα ligand, all-trans retinoic acid (ATRA), which results in the expression of genes that induce terminal granulocytic differentiation of the leukemic blasts. To investigate whether miRNA expression is regulated by ATRA in APL, we performed Taqman miRNA assays for 157 different mature miRNAs in the APL cell line NB4 before and after treatment with ATRA. We found that ATRA induced a more than 10 fold upregulation of 18 miRNAs and a more than 10 fold downregulation of 2 miRNAs. These expression patterns were confirmed in primary APL patient cells before and after treatment with ATRA. To study whether the miRNA expression pattern was dependent on the PML-RARα fusion protein, we used U937 cells stably transfected with a zinc-inducible PML-RARα expression cassette (U937PR9, a kind gift of Dr Pelicci). Upon ATRA treatment, we found that several miRNAs were only induced in the presence of PML-RARα, suggesting that PML-RARα is implicated in the expression of these miRNAs. To investigate whether the PML-RARα fusion protein binds to the endogenous miRNA genes chromatin immunoprecipitation assays were performed with PML-RARα transfected 293 cells. We demonstrated the presence of PML-RARα protein on the miRNA genes. This indicates that the oncoprotein PML-RARα directly influences the expression of these miRNAs. The function of the PML-RARα targeted miRNAs in APL cell differentiation is currently being studied using retroviral expression vectors.

scholarly journals Regulation of J6 gene expression by transcription factor GATA-4

1995 ◽  
Vol 307 (1) ◽  
pp. 183-189 ◽  
Author(s):  
M Bielinska ◽  
D B Wilson
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Binding Protein ◽  
Binding Studies ◽  
Protein Activity ◽  
Induced Differentiation ◽  
F9 Cells ◽  
F9 Embryonal Carcinoma Cells ◽  
Nih 3T3

Retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells into primitive endoderm is accompanied by increased transcription of the gene for J6, a heat shock protein implicated in collagen biosynthesis. In this paper we present evidence that transcription factor GATA-4, a retinoic acid-inducible GATA-binding protein, is involved in the regulation of J6 gene expression in F9 cells. Northern-blot analysis indicates that transcripts encoding GATA-4 and J6 increase in parallel during retinoic acid-induced differentiation of F9 cells. Gel-shift experiments and antibody binding studies demonstrate that: (1) GATA-4 is the major GATA-binding protein activity in differentiated F9 cells, and (2) GATA-4 binds to consensus GATA motifs in the retinoic acid-responsive portion of the J6 promoter. Co-transfection studies using NIH 3T3 cells show that GATA-4 is a potent trans-activator of the J6 promoter. These lines of evidence suggest that expression of J6 in F9 cells is regulated by GATA-4. We speculate that transcription factor GATA-4 may also control other genes involved in extracellular matrix formation in the yolk sac.

scholarly journals Matrix Metalloproteinase (MMP) 9 Transcription in Mouse Brain Induced by Fear Learning

2013 ◽  
Vol 288 (29) ◽  
pp. 20978-20991 ◽  
Author(s):  
Krishnendu Ganguly ◽  
Emilia Rejmak ◽  
Marta Mikosz ◽  
Evgeni Nikolaev ◽  
Ewelina Knapska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Prefrontal Cortex ◽  
Matrix Metalloproteinase ◽  
Gene Promoter ◽  
Brain Structures ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Contextual Fear ◽  
The Brain

Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, −42/-50- and −478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning.

scholarly journals Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.

1992 ◽  
Vol 12 (9) ◽  
pp. 4153-4163 ◽  
Author(s):  
A J Cooney ◽  
S Y Tsai ◽  
B W O'Malley ◽  
M J Tsai
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Dna Binding ◽  
Vitamin D3 ◽  
Retinoic Acid Receptors ◽  
Response Elements ◽  
Upstream Promoter ◽  
Chicken Ovalbumin

Alignment of natural chicken ovalbumin upstream promoter transcription factor (COUP-TF) response elements shows that, in addition to the predominant direct repeat of the GGTCA motif with a 2-bp spacing, there are other functional COUP elements with variations in the GGTCA orientation and spacing. We systematically analyzed the binding of in vitro-synthesized COUP-TFs and showed that COUP-TF is capable of binding to oligonucleotides containing both direct repeats and palindromes and with different spacings of the GGTCA repeats. Subsequently, we analyzed four possible mechanisms proposed to explain how COUP-TF could bind to these spatial variations of the GGTCA repeat. We demonstrated that the functional DNA-binding form of COUP-TF is a dimer which requires two GGTCA half-sites to bind DNA. We demonstrated that the COUP-TF dimer undergoes a remarkable structural adaptation to accommodate binding to these spatial variants of the GGTCA repeats. A functional consequence of the promiscuous DNA binding of COUP-TF is its ability to down-regulate hormonal induction of target gene expression by other members of the steroid-thyroid hormone receptor superfamily such as the vitamin D3, thyroid hormone, and retinoic acid receptors. Our data indicate that COUP-TF may have an important role in hormonal regulation of gene expression by these receptors.

Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors

1992 ◽  
Vol 12 (9) ◽  
pp. 4153-4163
Author(s):  
A J Cooney ◽  
S Y Tsai ◽  
B W O'Malley ◽  
M J Tsai
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Dna Binding ◽  
Vitamin D3 ◽  
Retinoic Acid Receptors ◽  
Response Elements ◽  
Upstream Promoter ◽  
Chicken Ovalbumin

Alignment of natural chicken ovalbumin upstream promoter transcription factor (COUP-TF) response elements shows that, in addition to the predominant direct repeat of the GGTCA motif with a 2-bp spacing, there are other functional COUP elements with variations in the GGTCA orientation and spacing. We systematically analyzed the binding of in vitro-synthesized COUP-TFs and showed that COUP-TF is capable of binding to oligonucleotides containing both direct repeats and palindromes and with different spacings of the GGTCA repeats. Subsequently, we analyzed four possible mechanisms proposed to explain how COUP-TF could bind to these spatial variations of the GGTCA repeat. We demonstrated that the functional DNA-binding form of COUP-TF is a dimer which requires two GGTCA half-sites to bind DNA. We demonstrated that the COUP-TF dimer undergoes a remarkable structural adaptation to accommodate binding to these spatial variants of the GGTCA repeats. A functional consequence of the promiscuous DNA binding of COUP-TF is its ability to down-regulate hormonal induction of target gene expression by other members of the steroid-thyroid hormone receptor superfamily such as the vitamin D3, thyroid hormone, and retinoic acid receptors. Our data indicate that COUP-TF may have an important role in hormonal regulation of gene expression by these receptors.

scholarly journals Retinoic acid production, regulation and containment through Zic1, Pitx2c and Cyp26c1 control cranial placode specification

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev193227
Author(s):  
Aditi Dubey ◽  
Jianshi Yu ◽  
Tian Liu ◽  
Maureen A. Kane ◽  
Jean-Pierre Saint-Jeannet
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Direct Measurement ◽  
Acid Production ◽  
Restricted Domain ◽  
Sensory Organs ◽  
Domain Specific ◽  
Common Precursor ◽  
Specific Manner

ABSTRACTAll paired sensory organs arise from a common precursor domain called the pre-placodal region (PPR). In Xenopus, Zic1 non-cell autonomously regulates PPR formation by activating retinoic acid (RA) production. Here, we have identified two Zic1 targets, the RA catabolizing enzyme Cyp26c1 and the transcription factor Pitx2c, expressed in the vicinity of the PPR as being crucially required for maintaining low RA levels in a spatially restricted, PPR-adjacent domain. Morpholino- or CRISPR/Cas9-mediated Cyp26c1 knockdown abrogated PPR gene expression, yielding defective cranial placodes. Direct measurement of RA levels revealed that this is mediated by a mechanism involving excess RA accumulation. Furthermore, we show that pitx2c is activated by RA and required for Cyp26c1 expression in a domain-specific manner through induction of FGF8. We propose that Zic1 anteriorly establishes a program of RA containment and regulation through activation of Cyp26c1 and Pitx2c that cooperates to promote PPR specification in a spatially restricted domain.

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis

2003 ◽  
Vol 48 (1) ◽  
pp. 134-145 ◽  
Author(s):  
Alpana Ray ◽  
Keiichi Kuroki ◽  
James L. Cook ◽  
B. Sonny Bal ◽  
Keith Kenter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 1
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