Reexamining the DNA target selectivity of Scalloped

Selector proteins are transcription factors that coordinate the formation and identity of organs and appendages. The proper formation of these tissues requires the selector proteins to regulate the expression of a large set of genes. Many selector proteins are involved in regulating multiple developmental processes, yet it is not completely clear how they are able to activate different sets of genes in a tissue-specific manner. An association with cofactors is thought to be one method by which enhancer selectivity is achieved. During wing development the selector protein Scalloped (SD) interacts with the cofactor Vestigial (VG). This interaction leads to the activation of a specific set of downstream wing genes. Herein, data are presented indicating that the switch in binding selectivity is likely achieved by VG altering the general affinity that the SD protein has for DNA. The decreased affinity for DNA is compensated for by the fact that the VG protein forms a complex containing two SD proteins. These two properties ensure that the SD–VG complex is able to bind only to enhancers that have two consecutive binding sites. Furthermore, data are presented that indicate that the function of the two terminal domains of the VG protein is not restricted to activating transcription and promoting the recruitment of two SD proteins.

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A proximal tissue-specific module and a distal negative regulatory module control apolipoprotein(a) gene transcription

Biochemical Journal ◽

10.1042/bj20030985 ◽

2004 ◽

Vol 379 (1) ◽

pp. 151-159 ◽

Cited By ~ 9

Author(s):

Sarita NEGI ◽

Saurabh K. SINGH ◽

Nirupma PATI ◽

Vikas HANDA ◽

Ruchi CHAUHAN ◽

...

Keyword(s):

Transcription Factors ◽

Gene Transcription ◽

Hela Cells ◽

Hepg2 Cells ◽

Regulatory Element ◽

Regulatory Elements ◽

Tissue Specific ◽

Apolipoprotein A ◽

Regulatory Module ◽

Specific Manner

The apo(a) [apolipoprotein(a)] gene is responsible for variations in plasma lipoprotein(a), high levels of which are a risk factor for atherosclerosis and myocardial infarction. The apo(a) promoter stimulates the expression of reporter genes in HepG2 cells, but not in HeLa cells. In the present study, we demonstrate that the 1.4 kb apo(a) promoter comprises two composite regulatory regions: a distal negative regulatory module (positions −1432 to −716) and a proximal tissue-specific module (−716 to −616). The distal negative regulatory module contains two strong negative regulatory regions [polymorphic PNR (pentanucleotide repeat region) and NREβ (negative regulatory element β)], which sandwich the postive regulatory region PREβ (positive regulatory element β). The PNR was shown to bind to transcription factors in a tissue-specific manner, whereas the ubiquitous transcription factors hepatocyte nuclear factor 3α and GATA binding protein 4 bound to NREβ to repress gene transcription. The proximal tissue-specific module contains two regulatory elements: an activating region (PREα) that activates transcription in HepG2 cells, and NREα, which is responsible for repressing the apo(a) gene in HeLa cells. NREα binds to a HeLa-specific repressor. These multiple regulatory elements might work co-operatively to finely regulate apo(a) gene expression. Although the tissue-specific module is required for apo(a) gene activation and repression in a tissue-specific manner, the combinatorial interplay of the distal and proximal regulators might define the complex pathway(s) of apo(a) gene regulation.

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Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes

BMC Genomics ◽

10.1186/1471-2164-7-133 ◽

2006 ◽

Vol 7 (1) ◽

Cited By ~ 132

Author(s):

Paz Polak ◽

Eytan Domany

Keyword(s):

Transcription Factors ◽

Binding Sites ◽

Developmental Processes ◽

Alu Elements

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Methylation of an ETS site in the intron enhancer of the keratin 18 gene participates in tissue-specific repression.

Molecular and Cellular Biology ◽

10.1128/mcb.17.9.4885 ◽

1997 ◽

Vol 17 (9) ◽

pp. 4885-4894 ◽

Cited By ~ 31

Author(s):

A Umezawa ◽

H Yamamoto ◽

K Rhodes ◽

M J Klemsz ◽

R A Maki ◽

...

Keyword(s):

Dna Methylation ◽

Transcription Factors ◽

Transgenic Mice ◽

Binding Site ◽

Binding Sites ◽

Epigenetic Modification ◽

Ets Transcription Factors ◽

Tissue Specific ◽

Mouse Tissues ◽

Keratin 18

The activities of ETS transcription factors are modulated by posttranscriptional modifications and cooperation with other proteins. Another factor which could alter the regulation of genes by ETS transcription factors is DNA methylation of their cognate binding sites. The optimal activity of the keratin 18 (K18) gene is dependent upon an ETS binding site within an enhancer region located in the first intron. The methylation of the ETS binding site was correlated with the repression of the K18 gene in normal human tissues and in K18 transgenic mouse tissues. Neither recombinant ETS2 nor endogenous spleen ETS binding activities bound the methylated site effectively. Increased expression of the K18 gene in spleens of transgenic mice by use of an alternative, cryptic promoter 700 bp upstream of the enhancer resulted in modestly decreased methylation of the K18 ETS site and increased RNA expression. Expression in transgenic mice of a mutant K18 gene, which was still capable of activation by ETS factors but was no longer a substrate for DNA methylation of the ETS site, was fivefold higher in spleen and heart. However, expression in other organs such as liver and intestine was similar to that of the wild-type gene. This result suggests that DNA methylation of the K18 ETS site may be functionally important in the tissue-specific repression of the K18 gene. Epigenetic modification of the binding sites for some ETS transcription factors may result in a refractory transcriptional response even in the presence of necessary trans-acting activities.

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Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene in erythroid cells is due to a tissue-specific 3' enhancer containing functionally important CACC/GT motifs and binding sites for GATA and Ets transcription factors.

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.868 ◽

1994 ◽

Vol 14 (1) ◽

pp. 868 ◽

Cited By ~ 1

Author(s):

J O'Prey ◽

S Ramsay ◽

I Chambers ◽

P R Harrison

Keyword(s):

Transcription Factors ◽

Glutathione Peroxidase ◽

Binding Sites ◽

Erythroid Cells ◽

Ets Transcription Factors ◽

Tissue Specific ◽

Peroxidase Gene ◽

Cytosolic Glutathione ◽

In Erythroid Cells

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CTCF: the protein, the binding partners, the binding sites and their chromatin loops

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0369 ◽

2013 ◽

Vol 368 (1620) ◽

pp. 20120369 ◽

Cited By ~ 108

Author(s):

Sjoerd Johannes Bastiaan Holwerda ◽

Wouter de Laat

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Rna Polymerase Ii ◽

Binding Sites ◽

Ctcf Binding ◽

Chromatin Domain ◽

Gene Promoters ◽

Tissue Specific ◽

Chromatin Loops ◽

Exact Function

CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved. It can act as a transcriptional activator, repressor and insulator, and it can pause transcription. CTCF binds at chromatin domain boundaries, at enhancers and gene promoters, and inside gene bodies. It can attract many other transcription factors to chromatin, including tissue-specific transcriptional activators, repressors, cohesin and RNA polymerase II, and it forms chromatin loops. Yet, or perhaps therefore, CTCF's exact function at a given genomic site is unpredictable. It appears to be determined by the associated transcription factors, by the location of the binding site relative to the transcriptional start site of a gene, and by the site's engagement in chromatin loops with other CTCF-binding sites, enhancers or gene promoters. Here, we will discuss genome-wide features of CTCF binding events, as well as locus-specific functions of this remarkable transcription factor.

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Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene in erythroid cells is due to a tissue-specific 3' enhancer containing functionally important CACC/GT motifs and binding sites for GATA and Ets transcription factors

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.868-.1994 ◽

1994 ◽

Vol 14 (1) ◽

pp. 868

Author(s):

J O'Prey ◽

S Ramsay ◽

I Chambers ◽

P R Harrison

Keyword(s):

Transcription Factors ◽

Glutathione Peroxidase ◽

Binding Sites ◽

Erythroid Cells ◽

Ets Transcription Factors ◽

Tissue Specific ◽

Peroxidase Gene ◽

Cytosolic Glutathione ◽

In Erythroid Cells

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A comprehensive manually-curated Compendium of Bovine Transcription Factors

10.1101/254011 ◽

2018 ◽

Author(s):

Marcela M de Souza ◽

Juan M Vaquerizas ◽

Adhemar Zerlotini ◽

Ludwig Geistlinger ◽

Benjamín Hernández-Rodríguez ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Regulation Of Gene Expression ◽

Regulatory Proteins ◽

Regulatory Mechanisms ◽

Domain Family ◽

Specific Expression ◽

Tissue Specific ◽

Control Gene Expression ◽

Specific Manner

ABSTRACTTranscription factors (TFs) are pivotal regulatory proteins that control gene expression in a context-dependent and tissue-specific manner. In contrast to human, where comprehensive curated TF collections exist, bovine TFs are only rudimentary recorded and characterized. In this article, we present a manually-curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we analyzed for domain family distribution, evolutionary conservation, and tissue-specific expression. In addition, we provide a list of putative transcription cofactors derived from known interactions with the identified TFs. Since there is a general lack of knowledge concerning the regulation of gene expression in cattle, the curated list of TF should provide a basis for an improved comprehension of regulatory mechanisms that are specific to the species.

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A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions

Cancers ◽

10.3390/cancers11091226 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1226 ◽

Cited By ~ 1

Author(s):

Herwig P. Moll ◽

Julian Mohrherr ◽

Leander Blaas ◽

Monica Musteanu ◽

Patricia Stiedl ◽

...

Keyword(s):

Transcription Factors ◽

Mouse Model ◽

Mouse Models ◽

Marked Reduction ◽

Genetically Engineered ◽

Tissue Specific ◽

Genetically Engineered Mouse Models ◽

Pharmacological Inhibition ◽

Specific Manner ◽

Health And Disease

Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. Stat3 and Stat5a/b transcription factors have been implicated in several pathophysiological conditions, and pharmacological inhibition of both transcription factors has been proposed to treat certain diseases, such as malignancies. To model combined inhibition of Stat3 and Stat5a/b we have developed a GEMM harboring a flox Stat3-Stat5a/b allele (Stat5/3loxP/loxP mice) and generated mice lacking Stat3 and Stat5a/b in hepatocytes (Stat5/3Δhep/Δhep). Stat5/3Δhep/Δhep mice exhibited a marked reduction of STAT3, STAT5A and STAT5B proteins in the liver and developed steatosis, a phenotype that resembles mice lacking Stat5a/b in hepatocytes. In addition, embryonic deletion of Stat3 and Stat5a/b (Stat5/3Δ/Δ mice) resulted in lethality, similar to Stat3Δ/Δ mice. This data illustrates that Stat5/3loxP/loxP mice are functional and can be used as a valuable tool to model the combined inhibition of Stat3 and Stat5a/b in tumorigenesis and other diseases.

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