Cement gland-specific activation of the Xag1 promoter is regulated by co-operation of putative Ets and ATF/CREB transcription factors

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4387-4397
Author(s):  
Fiona C. Wardle ◽  
Daniel H. Wainstock ◽  
Hazel L. Sive
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Site ◽  
Reporter Gene ◽  
Binding Sites ◽  
Cement Gland ◽  
Specific Expression ◽  
Necessary And Sufficient ◽  
Do So

The cement gland marks the extreme anterior ectoderm of the Xenopus embryo, and is determined through the overlap of several positional domains. In order to understand how these positional cues activate cement gland differentiation, the promoter of Xag1, a marker of cement gland differentiation, was analyzed. Previous studies have shown that Xag1 expression can be activated by the anterior-specific transcription factor Otx2, but that this activation is indirect. 102 bp of upstream genomic Xag1 sequence restricts reporter gene expression specifically to the cement gland. Within this region, putative binding sites for Ets and ATF/CREB transcription factors are both necessary and sufficient to drive cement gland-specific expression, and cooperate to do so. Furthermore, while the putative ATF/CREB factor is activated by Otx2, a factor acting through the putative Ets-binding site is not. These results suggest that Ets-like and ATF/CREB-like family members play a role in regulating Xag1 expression in the cement gland, through integration of Otx2 dependent and independent pathways.

scholarly journals The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

1994 ◽  
Vol 14 (11) ◽  
pp. 7517-7526 ◽  
Author(s):  
H S Ip ◽  
D B Wilson ◽  
M Heikinheimo ◽  
Z Tang ◽  
C N Ting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cardiac Muscle ◽  
Binding Site ◽  
Cardiac Myocytes ◽  
Specific Binding ◽  
Troponin C ◽  
Specific Gene ◽  
Cardiac Muscle Cells

The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.

scholarly journals POU domain transcription factor brain 4 confers pancreatic alpha-cell-specific expression of the proglucagon gene through interaction with a novel proximal promoter G1 element.

1997 ◽  
Vol 17 (12) ◽  
pp. 7186-7194 ◽  
Author(s):  
M A Hussain ◽  
J Lee ◽  
C P Miller ◽  
J F Habener
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Alpha Cell ◽  
Proximal Promoter ◽  
Major Constituent ◽  
Alpha Cells ◽  
Specific Expression ◽  
Pou Domain ◽  
Pancreatic Alpha Cell

The proglucagon gene is expressed in a highly restricted tissue-specific manner in the alpha cells of the pancreatic islet, the hypothalamus, and the small and large intestines. Proglucagon is processed to glucagon and glucagon-like peptides GLP-1 and -2. Glucagon is expressed in alpha cells and regulates glucose homeostasis. GLP-1 is implicated in the control of insulin secretion, food intake, and satiety signaling, and GLP-2 is implicated in regulating small-bowel growth. Cell-specific expression of the proglucagon gene is mediated by proteins that interact with the proximal G1 promoter element which contains several AT-rich domains with binding sites for homeodomain transcription factors. In an attempt to identify major homeodomain proteins involved in pancreatic alpha-cell-specific proglucagon expression, we found that the POU domain transcription factor brain 4 is abundantly expressed in proglucagon-producing islet cell lines and rat pancreatic islets. In the latter, brain 4 and glucagon immunoreactivity colocalize in the outer mantle of islets. Electrophoretic mobility shift assays with specific antisera identify brain 4 as a major constituent of nuclear proteins of glucagon-producing cells that bind to the G1 element of the proglucagon gene proximal promoter. Transcriptional transactivation experiments reveal that brain 4 is a major regulator of proglucagon gene expression by its interaction with the G1 element. The finding that a neuronal transcription factor is involved in glucagon gene transcription may explain the presence of proglucagon in certain areas of the brain as well as in pancreatic alpha cells. Further, this finding supports the idea that the neuronal properties of endodermis-derived endocrine pancreatic cells may find their basis in regulation of gene expression by neuronal transcription factors.

scholarly journals Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles

2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Human And Mouse

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.

scholarly journals Analysis of Activator and Repressor Functions Reveals the Requirements for Transcriptional Control by LuxR, the Master Regulator of Quorum Sensing in Vibrio harveyi

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Julia C. van Kessel ◽  
Luke E. Ulrich ◽  
Igor B. Zhulin ◽  
Bonnie L. Bassler
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Binding ◽  
Quorum Sensing ◽  
Binding Site ◽  
Binding Sites ◽  
Vibrio Harveyi ◽  
Communication Process ◽  
Nucleotide Sequencing ◽  
Collective Behaviors

ABSTRACT LuxR-type transcription factors are the master regulators of quorum sensing in vibrios. LuxR proteins are unique members of the TetR superfamily of transcription factors because they activate and repress large regulons of genes. Here, we used chromatin immunoprecipitation and nucleotide sequencing (ChIP-seq) to identify LuxR binding sites in the Vibrio harveyi genome. Bioinformatics analyses showed that the LuxR consensus binding site at repressed promoters is a symmetric palindrome, whereas at activated promoters it is asymmetric and contains only half of the palindrome. Using a genetic screen, we isolated LuxR mutants that separated activation and repression functions at representative promoters. These LuxR mutants exhibit sequence-specific DNA binding defects that restrict activation or repression activity to subsets of target promoters. Altering the LuxR DNA binding site sequence to one more closely resembling the ideal LuxR consensus motif can restore in vivo function to a LuxR mutant. This study provides a mechanistic understanding of how a single protein can recognize a variety of binding sites to differentially regulate gene expression. IMPORTANCE Bacteria use the cell-cell communication process called quorum sensing to regulate collective behaviors. In vibrios, LuxR-type transcription factors control the quorum-sensing gene expression cascade. LuxR-type proteins are structural homologs of TetR-type transcription factors. LuxR proteins were assumed to function analogously to TetR proteins, which typically bind to a single conserved binding site to repress transcription of one or two genes. We find here that unlike TetR proteins, LuxR acts a global regulator, directly binding upstream of and controlling more than 100 genes. Again unlike TetR, LuxR functions as both an activator and a repressor, and these two activities can be separated by mutagenesis. Finally, the consensus binding motifs driving LuxR-activated and -repressed genes are distinct. This work shows that LuxR, although structurally similar to TetR, has evolved unique features enabling it to differentially control a large regulon of genes in response to quorum-sensing cues.

scholarly journals target: an R package to predict combined function of transcription factors

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 344
Author(s):  
Mahmoud Ahmed ◽  
Deok Ryong Kim
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
R Package ◽  
Expression Data ◽  
Bioconductor Package ◽  
Chip Experiment ◽  
Binding Data ◽  
Two Factors

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the understanding of a transcription factor function. Here, we implemented the binding and expression target analysis (BETA) in an R/Bioconductor package. This algorithm ranks the targets based on the distances of their assigned peaks from the factor ChIP experiment and the signed statistics from gene expression profiling with factor perturbation. We further extend BETA to integrate two sets of data from two factors to predict their targets and their combined functions. In this article, we briefly describe the workings of the algorithm and provide a workflow with a real dataset for using it. The gene targets and the aggregate functions of transcription factors YY1 and YY2 in HeLa cells were identified. Using the same datasets, we identified the shared targets of the two factors, which were found to be, on average, more cooperatively regulated.

scholarly journals DeepGRN: Prediction of transcription factor binding site across cell-types using attention-based deep neural networks 

2021 ◽  
Author(s):  
Chen Chen ◽  
Jie Hou ◽  
Xiaowen Shi ◽  
Hua Yang ◽  
James A. Birchler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Site ◽  
Transcription Factor Binding Site ◽  
Dna Sequences ◽  
Binding Sites ◽  
Transcription Factor Binding ◽  
Parallel Sequencing ◽  
Factor Binding Site ◽  
Factor Binding

Abstract BackgroundDue to the complexity of the biological systems, the prediction of the potential DNA binding sites for transcription factors remains a difficult problem in computational biology. Genomic DNA sequences and experimental results from parallel sequencing provide available information about the affinity and accessibility of genome and are commonly used features in binding sites prediction. The attention mechanism in deep learning has shown its capability to learn long-range dependencies from sequential data, such as sentences and voices. Until now, no study has applied this approach in binding site inference from massively parallel sequencing data. The successful applications of attention mechanism in similar input contexts motivate us to build and test new methods that can accurately determine the binding sites of transcription factors.ResultsIn this study, we propose a novel tool (named DeepGRN) for transcription factors binding site prediction based on the combination of two components: single attention module and pairwise attention module. The performance of our methods is evaluated on the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge datasets. The results show that DeepGRN achieves higher unified scores in 6 of 13 targets than any of the top four methods in the DREAM challenge. We also demonstrate that the attention weights learned by the model are correlated with potential informative inputs, such as DNase-Seq coverage and motifs, which provide possible explanations for the predictive improvements in DeepGRN.ConclusionsDeepGRN can automatically and effectively predict transcription factor binding sites from DNA sequences and DNase-Seq coverage. Furthermore, the visualization techniques we developed for the attention modules help to interpret how critical patterns from different types of input features are recognized by our model.

Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi-1/PU.1.

1995 ◽  
Vol 15 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Y Kominato ◽  
D Galson ◽  
W R Waterman ◽  
A C Webb ◽  
P E Auron
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Reporter Gene ◽  
Expression Vector ◽  
Dominant Negative ◽  
Specific Factor ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Interleukin-1 beta (IL-1 beta) is produced primarily by stimulated monocytes, suggesting that the IL1B gene, which codes for this protein, depends upon at least one cell-type-specific factor. Our previous characterization of the IL1B promoter indicated that the region between -131 and +12 is sufficient to direct cell-type-specific expression of a reporter gene (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M.J. Fenton, A.C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). We now show that a sequence located between positions -50 and -39 of the IL1B promoter binds the tissue-restricted Ets domain transcription factor Spi-1/PU.1 (Spi-1). Mutation of this site abrogates binding of this factor and reduces the ability of the IL1B promoter to function in macrophages. A second Spi-1 binding site located between positions -115 and -97 also is required for maximal IL1B promoter activity in the presence of the proximal Spi-1 binding site. In addition, an activation domain-deficient Spi-1 expression vector acts as a dominant-negative inhibitor of reporter gene expression in a monocyte cell line. Finally, the IL1B promoter, which is inactive in Spi-1-deficient HeLa cells, is activated in these cells by cotransfection with a Spi-1 expression vector. Thus, the cell-type-specific expression of the IL1B promoter appears to be dependent on the binding of Spi-1.

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells

1994 ◽  
Vol 14 (11) ◽  
pp. 7517-7526
Author(s):  
H S Ip ◽  
D B Wilson ◽  
M Heikinheimo ◽  
Z Tang ◽  
C N Ting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cardiac Muscle ◽  
Binding Site ◽  
Cardiac Myocytes ◽  
Specific Binding ◽  
Troponin C ◽  
Specific Gene ◽  
Cardiac Muscle Cells

The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.

scholarly journals Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element

2005 ◽  
Vol 25 (7) ◽  
pp. 2832-2845 ◽  
Author(s):  
Yutaka Okuno ◽  
Gang Huang ◽  
Frank Rosenbauer ◽  
Erica K. Evans ◽  
Hanna S. Radomska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Reporter Gene ◽  
Regulatory Element ◽  
Mammalian Species ◽  
Critical Role ◽  
Homologous Region ◽  
Specific Expression ◽  
Upstream Regulatory Element

ABSTRACT Regulation of the hematopoietic transcription factor PU.1 (Spi-1) plays a critical role in the development of white cells, and abnormal expression of PU.1 can lead to leukemia. We previously reported that the PU.1 promoter cannot induce expression of a reporter gene in vivo, and cell-type-specific expression of PU.1 in stable lines was conferred by a 3.4-kb DNA fragment including a DNase I hypersensitive site located 14 kb upstream of the transcription start site. Here we demonstrate that this kb −14 site confers lineage-specific reporter gene expression in vivo. This kb −14 upstream regulatory element contains two 300-bp regions which are highly conserved in five mammalian species. In Friend virus-induced erythroleukemia, the spleen focus-forming virus integrates into the PU.1 locus between these two conserved regions. DNA binding experiments demonstrated that PU.1 itself and Elf-1 bind to a highly conserved site within the proximal homologous region in vivo. A mutation of this site abolishing binding of PU.1 and Elf-1 led to a marked decrease in the ability of this upstream element to direct activity of reporter gene in myelomonocytic cell lines. These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression.

scholarly journals Regulation of IκBβ Expression in Testis

2002 ◽  
Vol 13 (12) ◽  
pp. 4179-4194 ◽  
Author(s):  
Lucy M. Budde ◽  
Chun Wu ◽  
Christopher Tilman ◽  
Iris Douglas ◽  
Sankar Ghosh
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Reporter Gene ◽  
Binding Sites ◽  
Potential Role ◽  
Nuclear Factor Κb ◽  
Transient Transfection ◽  
Nuclear Factor ◽  
Transcription Factor Family ◽  
Novel Target

IκBα and IκBβ are regulators of the nuclear factor-κB (NF-κB) transcription factor family. Both IκBs bind to the same NF-κB dimers and are widely expressed in different cells and tissues. To better understand how these two IκB isoforms differ biologically, we have characterized the expression of IκBβ in testis, a tissue in which IκBα is only minimally expressed. We have found that IκBβ expression is localized within the haploid spermatid stages of spermatogenesis and follows the expression of nuclear NF-κB. IκBβ expression in haploid spermatids is likely regulated by Sox family proteins, members of which are also expressed within spermatids. We have shown that both SRY and Sox-5 can bind to multiple Sox binding sites found within the IκBβ promoter and can enhance transcription of a reporter gene in transient transfection assays. We also demonstrate that IκBβ mRNA is strongly expressed in developing male gonads. These results therefore suggest that IκBβ may be a novel target for transcription factors of the HMG-box SRY/Sox family and imply a potential role for NF-κB/IκBβ in spermatogenesis.

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