Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors

The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor regulates extracellular calcium concentrations and is therefore important for mineral homeostasis. ROS 17/2.8 cells, a rat osteoblast-like osteosarcoma cell line, express the PTH/PTHrP receptor and provide a good model for examining the transcriptional regulation of its gene. The rat PTH/PTHrP receptor gene has two promoters, U1 and U3, which were shown to be important for its expression. Using extracts from ROS 17/2.8 cells, we have demonstrated two regions (termed FP1 and FP2) of nuclear protein/DNA interaction within promoter sequences previously shown to be important for the activity of the U3 promoter. Nuclear extracts from rat 2 fibroblasts, which do not express the PTH/PTHrP receptor, produced one site of protein/DNA interaction which was found at a position on the promoter identical to the position of FP1 produced by a ROS 17/2.8 nuclear extract. Mutation of these two sites of protein/DNA interaction resulted in reduced U3 promoter activity. Furthermore, we have demonstrated that the transcription factors SP1 and MAZ regulate U3 promoter expression and have shown their functional significance using mutational analysis. These data demonstrate that SP1 and MAZ bind to the PTH/PTHrP receptor promoter and that they are involved in cell-specific expression of its gene product.

Download Full-text

Synergistic interactions between transcription factors control expression of the apolipoprotein AI gene in liver cells

Molecular and Cellular Biology ◽

10.1128/mcb.11.2.677-687.1991 ◽

1991 ◽

Vol 11 (2) ◽

pp. 677-687

Author(s):

R L Widom ◽

J A Ladias ◽

S Kouidou ◽

S K Karathanasis

Keyword(s):

Transcription Factors ◽

Hepg2 Cells ◽

Liver Cells ◽

Site Directed Mutagenesis ◽

Apolipoprotein Ai ◽

Transcriptional Enhancer ◽

Specific Expression ◽

Cis Acting ◽

Synergistic Interactions ◽

Gene Coding

The gene coding for apolipoprotein AI (apoAI), a plasma protein involved in the transport of cholesterol and other lipids in the plasma, is expressed predominantly in liver and intestine. Previous work in our laboratory has shown that different cis-acting elements in the 5'-flanking region of the human apoAI gene control its expression in human hepatoma (HepG2) and colon carcinoma (Caco-2) cells. Hepatocyte-specific expression is mediated by elements within the -256 to -41 DNA region relative to the apoAI gene transcription start site (+1). In this study it was found that the -222 to -110 apoAI gene region is necessary and sufficient for expression in HepG2 cells. It was also found that this DNA region functions as a powerful hepatocyte-specific transcriptional enhancer. Gel retardation and DNase I protection experiments showed that HepG2 cells contain proteins that bind to specific sites, sites A (-214 to -192), B (-169 to -146), and C (-134 to -119), within this enhancer. Site-directed mutagenesis that prevents binding of these proteins to individual or different combinations of these sites followed by functional analysis of these mutants in HepG2 cells revealed that protein binding to any one of these sites in the absence of binding to the others was not sufficient for expression. Binding to any two of these sites in any combination was sufficient for only low levels of expression. Binding to all three sites was essential for maximal expression. These results indicate that the transcriptional activity of the apoAI gene in liver cells is dependent on synergistic interactions between transcription factors bound to its enhancer.

Download Full-text

The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families

Molecular and Cellular Biology ◽

10.1128/mcb.13.7.3860-3871.1993 ◽

1993 ◽

Vol 13 (7) ◽

pp. 3860-3871

Author(s):

P L Sawaya ◽

B R Stripp ◽

J A Whitsett ◽

D S Luse

Keyword(s):

Transcription Factors ◽

Rat Liver ◽

Transcription Initiation ◽

Clara Cell ◽

Clara Cells ◽

Mobility Shift ◽

Specific Expression ◽

Fetal Sheep ◽

Region I

We have shown that a large fragment (-2339 to +57) from the rat CC10 gene directed lung-specific expression of a reporter construct in transgenic animals. Upon transfection, a smaller fragment (-165 to +57) supported reporter gene expression exclusively in the Clara cell-like NCI-H441 cell line, suggesting that a Clara cell-specific transcriptional element resided on this fragment (B. R. Stripp, P. L. Sawaya, D. S. Luse, K. A. Wikenheiser, S. E. Wert, J. A. Huffman, D. L. Lattier, G. Singh, S. L. Katyal, and J. A. Whitsett, J. Biol. Chem. 267:14703-14712, 1992). The interactions of nuclear proteins with a particular segment of the CC10 promoter which extends from 79 to 128 bp upstream of the CC10 transcription initiation site (CC10 region I) have now been studied. This sequence can stimulate both in vitro transcription in H441 nuclear extract and transient expression of reporter constructs in H441 cells. Electrophoretic mobility shift assays using extracts from H441, HeLa, rat liver, and fetal sheep lung cells were used to demonstrate that members of the AP-1, octamer, and HNF-3 families bind to CC10 region I. Transcription factors from H441 cells which are capable of binding to CC10 region I are either absent in HeLa, rat liver, and fetal sheep lung extracts or enriched in H441 extracts relative to extracts from non-Clara cells.

Download Full-text

Regulation of rice root development by a retrotransposon acting as a microRNA sponge

eLife ◽

10.7554/elife.30038 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 23

Author(s):

Jungnam Cho ◽

Jerzy Paszkowski

Keyword(s):

Gene Regulation ◽

Transcription Factors ◽

Root Development ◽

Binding Sites ◽

Transcriptional Control ◽

Specific Expression ◽

Ability To Act ◽

Specific Accumulation ◽

In Trans ◽

Microrna Sponge

It is well documented that transposable elements (TEs) can regulate the expression of neighbouring genes. However, their ability to act in trans and influence ectopic loci has been reported rarely. We searched in rice transcriptomes for tissue-specific expression of TEs and found them to be regulated developmentally. They often shared sequence homology with co-expressed genes and contained potential microRNA-binding sites, which suggested possible contributions to gene regulation. In fact, we have identified a retrotransposon that is highly transcribed in roots and whose spliced transcript constitutes a target mimic for miR171. miR171 destabilizes mRNAs encoding the root-specific family of SCARECROW-Like transcription factors. We demonstrate that retrotransposon-derived transcripts act as decoys for miR171, triggering its degradation and thus results in the root-specific accumulation of SCARECROW-Like mRNAs. Such transposon-mediated post-transcriptional control of miR171 levels is conserved in diverse rice species.

Download Full-text

Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize

10.1101/2021.02.05.429970 ◽

2021 ◽

Author(s):

Mingxia Zhao ◽

Zhao Peng ◽

Yang Qin ◽

Ling Zhang ◽

Bin Tian ◽

...

Keyword(s):

Gene Regulation ◽

Transcription Factor ◽

Transcription Factors ◽

Protein Delivery ◽

Graphical Model ◽

Gene Activation ◽

Cuticular Wax ◽

Host Cells ◽

Myb Transcription Factor ◽

Leaf Phenotype

ABSTRACTCellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the γ-proteobacterium genus Xanthomonas and secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen, Xanthomonas vasicola pv. vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize gene glossy3 (gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146 gl3 downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68 gl3 downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from the gl3 downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.

Download Full-text

DNA Binding and Gene Activation Properties of the Nmp4 Nuclear Matrix Transcription Factors

Journal of Biological Chemistry ◽

10.1074/jbc.m107496200 ◽

2002 ◽

Vol 277 (18) ◽

pp. 16153-16159 ◽

Cited By ~ 21

Author(s):

Kitti Torrungruang ◽

Marta Alvarez ◽

Rita Shah ◽

Jude E. Onyia ◽

Simon J. Rhodes ◽

...

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Nuclear Matrix ◽

Gene Activation

Download Full-text

Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors

Molecular Biology of the Cell ◽

10.1091/mbc.e05-08-0775 ◽

2006 ◽

Vol 17 (2) ◽

pp. 585-597 ◽

Cited By ~ 36

Author(s):

Fang Liu ◽

Nabendu Pore ◽

Mijin Kim ◽

K. Ranh Voong ◽

Melissa Dowling ◽

...

Keyword(s):

Transcription Factors ◽

Dna Sequences ◽

Chromatin Immunoprecipitation ◽

Histone Deacetylases ◽

Targeted Mutagenesis ◽

Cellular Functions ◽

Specific Expression ◽

Protein Levels ◽

Histone Deacetylase 4 ◽

First Time

Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4.

Download Full-text

Transcript profiling of bovine embryos implicates specific transcription factors in the maternal-to-embryo transition

Biology of Reproduction ◽

10.1093/biolre/ioz209 ◽

2019 ◽

Vol 102 (3) ◽

pp. 671-679 ◽

Cited By ~ 3

Author(s):

Yanina S Bogliotti ◽

Nhi Chung ◽

Erika E Paulson ◽

James Chitwood ◽

Michelle Halstead ◽

...

Keyword(s):

Transcription Factors ◽

Rna Polymerase Ii ◽

Gene Activation ◽

Preimplantation Embryos ◽

Maternal Mrna ◽

Embryonic Genome ◽

Maternal Mrnas ◽

Low Levels ◽

Genome Activation ◽

Further Development

Abstract Full-grown oocytes are transcriptionally quiescent. Following maturation and fertilization, the early stages of embryonic development occur in the absence (or low levels) of transcription that results in a period of development relying on maternally derived products (e.g., mRNAs and proteins). Two critical steps occur during the transition from maternal to embryo control of development: maternal mRNA clearance and embryonic genome activation with an associated dramatic reprogramming of gene expression required for further development. By combining an RNA polymerase II inhibitor with RNA sequencing, we were able not only to distinguish maternally derived from embryonic transcripts in bovine preimplantation embryos but also to establish that embryonic gene activation is required for clearance of maternal mRNAs as well as to identify putative transcription factors that are likely critical for early bovine development.

Download Full-text

EMT-Inducing Transcription Factors, Drivers of Melanoma Phenotype Switching, and Resistance to Treatment

Cancers ◽

10.3390/cancers12082154 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2154 ◽

Cited By ~ 2

Author(s):

Yaqi Tang ◽

Simon Durand ◽

Stéphane Dalle ◽

Julie Caramel

Keyword(s):

Transcription Factors ◽

Neural Crest ◽

Epithelial Mesenchymal Transition ◽

Expression Patterns ◽

Specific Expression ◽

Therapeutic Targeting ◽

Mesenchymal Transition ◽

Neural Crest Stem Cell ◽

Resistance To Treatment ◽

Phenotype Switching

Transcription factors, extensively described for their role in epithelial–mesenchymal transition (EMT-TFs) in epithelial cells, also display essential functions in the melanocyte lineage. Recent evidence has shown specific expression patterns and functions of these EMT-TFs in neural crest-derived melanoma compared to carcinoma. Herein, we present an update of the specific roles of EMT-TFs in melanocyte differentiation and melanoma progression. As major regulators of phenotype switching between differentiated/proliferative and neural crest stem cell-like/invasive states, these factors appear as major drivers of intra-tumor heterogeneity and resistance to treatment in melanoma, which opens new avenues in terms of therapeutic targeting.

Download Full-text