scholarly journals A Novel Role for the Forkhead Transcription Factor FOXL2 in Activin A-Regulated Follicle-Stimulating Hormone β Subunit Transcription

2009 ◽  
Vol 23 (7) ◽  
pp. 1001-1013 ◽  
Author(s):  
Pankaj Lamba ◽  
Jérôme Fortin ◽  
Stella Tran ◽  
Ying Wang ◽  
Daniel J. Bernard
Keyword(s):  
Transcription Factor ◽  
Base Pair ◽  
Activin A ◽  
Proximal Promoter ◽  
Comparative Approach ◽  
Forkhead Transcription Factor ◽  
Endogenous Protein ◽  
Highly Sensitive ◽  
Close Proximity ◽  
Single Base Pair

Abstract Selective synthesis and release of FSH from pituitary gonadotropes is regulated by activins. Activins directly stimulate murine FSHβ (Fshb) subunit gene transcription through a consensus 8-bp Sma- and Mad-related protein-binding element (SBE) in the proximal promoter. In contrast, the human FSHB promoter is relatively insensitive to the direct effects of activins and lacks this SBE. The proximal porcine Fshb promoter, which is highly conserved with human, similarly lacks the 8-bp SBE, but is nonetheless highly sensitive to activins. We used a comparative approach to determine mechanisms mediating differential activin induction of human, porcine, and murine Fshb/FSHB promoters. We mapped an activin response element in the proximal porcine promoter and identified interspecies variation in a single base pair in close proximity that conferred strong binding of the forkhead transcription factor FOXL2 to the porcine, but not human or murine, promoters. Introduction of the human base pair into the porcine promoter abolished FOXL2 binding and activin A induction. FOXL2 conferred activin A induction to the porcine promoter in heterologous cells, whereas knockdown of the endogenous protein in gonadotropes inhibited the activin A response. The murine Fshb promoter lacks the high-affinity FOXL2-binding site, but its activin induction is FOXL2 sensitive. We identified a more proximal FOXL2-binding element in the murine promoter, which is conserved across species. Mutation of this site attenuated activin A induction of both the porcine and murine promoters. Collectively, the data indicate a novel role for FOXL2 in activin A-regulated Fshb transcription.

Tc, an unusual promoter element required for constitutive transcription of the yeast HIS3 gene

1990 ◽  
Vol 10 (9) ◽  
pp. 4447-4455
Author(s):  
S Mahadevan ◽  
K Struhl
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Base Pair ◽  
Point Mutations ◽  
Proximal Promoter ◽  
Promoter Element ◽  
Tata Element ◽  
Typical Sequence ◽  
His3 Gene ◽  
Transcriptional Stimulation

Tc is the proximal promoter element required for constitutive his3 transcription that occurs in the absence of the canonical TATA element (TR) and is initiated from the +1 site. The TC element, unlike TR, does not respond to transcriptional stimulation by the GCN4 or GAL4 activator protein. Analysis of deletion, substitution, and point mutations indicates that Tc mapped between nucleotides -54 and -83 and is a sequence-dependent element because it could not be functionally replaced by other DNA sequences. However, in contrast to the behavior of typical promoter elements, it was surprisingly difficult to eliminate Tc function by base pair substitutions. Of 15 derivatives averaging four substitutions in the Tc region and representing 40% of all possible single changes, only 1 inactivated the Tc element. Moreover, the phenotypes of mutant and hybrid elements indicated that inactivation of Tc required multiple changes. The spacing between Tc and the initiation region could be varied over a 30-base-pair range without significantly affecting the level of transcription from the +1 site. From these results, we consider it possible that Tc may not interact with TFIID or some other typical sequence-specific transcription factor, but instead might influence transcription, either directly or indirectly, by its DNA structure.

scholarly journals Base-pair resolution detection of transcription factor binding site by deep deconvolutional network

2018 ◽  
Author(s):  
Sirajul Salekin ◽  
Jianqiu (Michelle) Zhang ◽  
Yufei Huang
Keyword(s):  
Transcription Factor ◽  
Base Pair ◽  
De Novo ◽  
Learning Algorithm ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Deep Learning Algorithm ◽  
Single Base Pair ◽  
Regulatory Analysis ◽  
Nucleotide Resolution

AbstractMotivationTranscription factor (TF) binds to the promoter region of a gene to control gene expression. Identifying precise transcription factor binding sites (TFBS) is essential for understanding the detailed mechanisms of TF mediated gene regulation. However, there is a shortage of computational approach that can deliver single base pair (bp) resolution prediction of TFBS.ResultsIn this paper, we propose DeepSNR, a Deep Learning algorithm for predicting transcription factor binding location at Single Nucleotide Resolution de novo from DNA sequence. DeepSNR adopts a novel deconvolutional network (deconvNet) model and is inspired by the similarity to image segmentation by deconvNet. The proposed deconvNet architecture is constructed on top of ‘Deep-Bind’ and we trained the entire model using TF specific data from ChIP-exonuclease (ChIP-exo) experiments. DeepSNR has been shown to outperform motif search based methods for several evaluation metrics. We have also demonstrated the usefulness of DeepSNR in the regulatory analysis of TFBS as well as in improving the TFBS prediction specificity using ChIP-seq data.AvailabilityDeepSNR is available open source in the GitHub repository (https://github.com/sirajulsalekin/DeepSNR)[email protected]

scholarly journals Tc, an unusual promoter element required for constitutive transcription of the yeast HIS3 gene.

1990 ◽  
Vol 10 (9) ◽  
pp. 4447-4455 ◽  
Author(s):  
S Mahadevan ◽  
K Struhl
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Base Pair ◽  
Point Mutations ◽  
Proximal Promoter ◽  
Promoter Element ◽  
Tata Element ◽  
Typical Sequence ◽  
His3 Gene ◽  
Transcriptional Stimulation

Tc is the proximal promoter element required for constitutive his3 transcription that occurs in the absence of the canonical TATA element (TR) and is initiated from the +1 site. The TC element, unlike TR, does not respond to transcriptional stimulation by the GCN4 or GAL4 activator protein. Analysis of deletion, substitution, and point mutations indicates that Tc mapped between nucleotides -54 and -83 and is a sequence-dependent element because it could not be functionally replaced by other DNA sequences. However, in contrast to the behavior of typical promoter elements, it was surprisingly difficult to eliminate Tc function by base pair substitutions. Of 15 derivatives averaging four substitutions in the Tc region and representing 40% of all possible single changes, only 1 inactivated the Tc element. Moreover, the phenotypes of mutant and hybrid elements indicated that inactivation of Tc required multiple changes. The spacing between Tc and the initiation region could be varied over a 30-base-pair range without significantly affecting the level of transcription from the +1 site. From these results, we consider it possible that Tc may not interact with TFIID or some other typical sequence-specific transcription factor, but instead might influence transcription, either directly or indirectly, by its DNA structure.

A Single Base Pair Deletion in the Promoter Region of the Factor IX Gene Is Associated with Haemophilia B

1994 ◽  
Vol 72 (06) ◽  
pp. 799-803 ◽  
Author(s):  
Adrian J Hall ◽  
Ampaiwan Chuansumrit ◽  
Ian R Peake ◽  
Peter R Winship
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Base Pair ◽  
Factor Ix ◽  
Single Base ◽  
Haemophilia B ◽  
Base Pair Deletion ◽  
Patient Reported ◽  
Single Base Pair ◽  
Factor C

SummaryPatients with the haemophilia B Leyden phenotype show a distinct pattern of factor IX expression characterized by a post-pubertal increase in FIX levels and the remission of clinical symptoms in adult life. This phenotype has previously been linked to single base mutations within transcription factor binding sites in a region of ∼40 bp around the major start point of transcription of the FIX gene. Here we report a novel mutation in this region within the transcription factor C/EBP binding site at +1 to +18. The mutation is a single base pair deletion from a triplet of thymine residues at +6 to +8. We show that the extent to which this mutation disrupts the binding of C/EBP to its binding site is less marked than the disruption caused by the +13 A→G mutation of FIX Norwich (1). This correlates with age-matched phenotypic data we have available for the patient reported here and that of FIX Norwich.

scholarly journals Activin A Regulates Porcine Follicle-Stimulating Hormone β-Subunit Transcription via Cooperative Actions of SMADs and FOXL2

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5456-5467 ◽  
Author(s):  
Pankaj Lamba ◽  
Ying Wang ◽  
Stella Tran ◽  
Tamara Ouspenskaia ◽  
Vanessa Libasci ◽  
...  
Keyword(s):  
Binding Sites ◽  
Activin A ◽  
Proximal Promoter ◽  
Nuclear Accumulation ◽  
General Mechanism ◽  
Cis Elements ◽  
Forkhead Transcription Factor ◽  
Activation Of Transcription ◽  
Smad Proteins ◽  
Form Part

Activins stimulate FSH synthesis and secretion by pituitary gonadotrope cells. Activin A induction of porcine and murine FSHβ (Fshb) gene transcription in immortalized gonadotropes is dependent on homolog of Drosophila mothers against decapentaplegic (SMAD) proteins as well as the forkhead transcription factor L2 (FOXL2). Using both heterologous and homologous cell models, we demonstrate that FOXL2 functionally synergizes with SMAD3/4 to stimulate porcine Fshb promoter-reporter activity. We further show that endogenous FOXL2 and SMAD2/3 physically interact in homologous cells. We identify two composite cis-elements of adjacent FOXL2 and SMAD binding sites in the proximal porcine Fshb promoter that mediate activin A, FOXL2, and SMAD3 actions. FOXL2 can bind these elements independently of SMADs, whereas SMAD3/4 binding requires high-affinity FOXL2 binding. Conversely, FOXL2 alone is insufficient to regulate Fshb transcription and requires SMADs to induce promoter activity. Collectively, our data suggest a model in which activins stimulate formation and nuclear accumulation of SMAD3/4 complexes, which interact with FOXL2 bound to at least two proximal promoter elements. This association stabilizes SMAD3/4 binding to adjacent SMAD binding elements. SMAD-FOXL2 complexes then mediate activation of transcription through a currently unknown mechanism. Conservation of one of the two composite cis-elements suggests that this may form part of a general mechanism whereby activins regulate Fshb subunit transcription and FSH synthesis.

scholarly journals Usefulness of BATF3 Immunohistochemistry in Diagnosing Classical Hodgkin Lymphoma

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1123
Author(s):  
Julian Benckendorff ◽  
Johanna Kuchar ◽  
Frank Leithäuser ◽  
Malena Zahn ◽  
Peter Möller
Keyword(s):  
Transcription Factor ◽  
Western Blot ◽  
Hodgkin Lymphoma ◽  
Anaplastic Large Cell Lymphoma ◽  
Diagnostic Marker ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Classical Hodgkin Lymphoma ◽  
Highly Sensitive ◽  
Large Cell Lymphoma

It is well recognized that the AP-1 transcription factor BATF3 is constitutively expressed in Hodgkin/Reed-Sternberg (HRS) cells, but its potential as a diagnostic marker for classical Hodgkin lymphoma (cHL) has not yet been addressed. In this study, we performed immunohistochemistry and analyzed the BATF3 expression in lymphoma cells on 218 lymphoma samples belonging to 14 different lymphoma entities. We observed varying degrees of BATF3 expression in nearly half of the cases (n = 100) with BATF3 expression being a constitutive feature of cHL (n = 53) and anaplastic large cell lymphoma (ALCL). By scoring BATF3 expression (BATF3-score) we observed constitutively high BATF3-scores in cHL and ALCL and low to moderate BATF3-scores in all other entities examined. Western blot analysis confirmed BATF3 protein expression in cell lysates from cHL cell lines (n = 7). Thus, BATF3 can be considered a useful IHC marker for the diagnosis of cHL as it is highly sensitive and sufficiently specific when analyzed by BATF3-scoring.

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