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The FEBS Journal Jan 2015For many years, transcription factor Sp1 was viewed as a basal transcription factor and relegated to a role in the regulation of so-called housekeeping genes.... (Review)
Review
For many years, transcription factor Sp1 was viewed as a basal transcription factor and relegated to a role in the regulation of so-called housekeeping genes. Identification of Sp1's role in recruiting the general transcription machinery in the absence of a TATA box increased its importance in gene regulation, particularly in light of recent estimates that the majority of mammalian genes lack a TATA box. In this review, we briefly consider the history of Sp1, the founding member of the Sp family of transcription factors. We review the evidence suggesting that Sp1 is highly regulated by post-translational modifications that positively and negatively affect the activity of Sp1 on a wide array of genes. Sp1 is over-expressed in many cancers and is associated with poor prognosis. Targeting Sp1 in cancer treatment has been suggested; however, our review of the literature on the role of Sp1 in the regulation of genes that contribute to the 'hallmarks of cancer' illustrates the extreme complexity of Sp1 functions. Sp1 both activates and suppresses the expression of a number of essential oncogenes and tumor suppressors, as well as genes involved in essential cellular functions, including proliferation, differentiation, the DNA damage response, apoptosis, senescence and angiogenesis. Sp1 is also implicated in inflammation and genomic instability, as well as epigenetic silencing. Given the apparently opposing effects of Sp1, a more complete understanding of the function of Sp1 in cancer is required to validate its potential as a therapeutic target.
Topics: Apoptosis; Cell Differentiation; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Molecular Targeted Therapy; Neoplasms; Protein Processing, Post-Translational; Sp1 Transcription Factor; TATA Box; Transcription, Genetic
PubMed: 25393971
DOI: 10.1111/febs.13148 -
Molecular Cell Sep 2021RNA polymerase II (RNA Pol II) transcription reconstituted from purified factors suggests pre-initiation complexes (PICs) can assemble by sequential incorporation of...
RNA polymerase II (RNA Pol II) transcription reconstituted from purified factors suggests pre-initiation complexes (PICs) can assemble by sequential incorporation of factors at the TATA box. However, these basal transcription reactions are generally independent of activators and co-activators. To study PIC assembly under more realistic conditions, we used single-molecule microscopy to visualize factor dynamics during activator-dependent reactions in nuclear extracts. Surprisingly, RNA Pol II, TFIIF, and TFIIE can pre-assemble on enhancer-bound activators before loading into PICs, and multiple RNA Pol II complexes can bind simultaneously to create a localized cluster. Unlike TFIIF and TFIIE, TFIIH binding is singular and dependent on the basal promoter. Activator-tethered factors exhibit dwell times on the order of seconds. In contrast, PICs can persist on the order of minutes in the absence of nucleotide triphosphates, although TFIIE remains unexpectedly dynamic even after TFIIH incorporation. Our kinetic measurements lead to a new branched model for activator-dependent PIC assembly.
Topics: Cell Nucleus; Mediator Complex; Promoter Regions, Genetic; RNA Polymerase II; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Single Molecule Imaging; TATA Box; TATA-Box Binding Protein; Transcription Factor TFIIH; Transcription Factors, TFII; Transcription Initiation, Genetic; Transcription, Genetic
PubMed: 34384542
DOI: 10.1016/j.molcel.2021.07.025 -
Biochemistry. Biokhimiia Feb 2009TATA-binding protein (TBP) is the first basal factor that recognizes and binds a TATA box on TATA-containing gene promoters transcribed by RNA polymerase II. Data... (Review)
Review
TATA-binding protein (TBP) is the first basal factor that recognizes and binds a TATA box on TATA-containing gene promoters transcribed by RNA polymerase II. Data available in the literature are indicative of admissible variability of the TATA box. The TATA box flanking sequences can influence TBP affinity as well as the level of basal and activated transcription. The possibility of mediated involvement in in vivo gene expression regulation of the TBP interactions with variant TATA boxes is supported by data on TATA box polymorphisms and associated human hereditary pathologies. A table containing data on TATA element polymorphisms in human gene promoters (about 40 mutations have been described), associated with particular pathologies, their short functional characteristics, and manifestation mechanisms of TATA-box SNPs is presented. Four classes of polymorphisms are considered: TATA box polymorphisms that weaken and enhance promoter, polymorphisms causing TATA box emergence and disappearance, and human virus TATA box polymorphisms. The described examples are indicative of the polymorphism-associated severe pathologies like thalassemia, the increased risk of hepatocellular carcinoma, sensitivity to H. pylori infection, oral cavity and lung cancers, arterial hypertension, etc.
Topics: Genetic Diseases, Inborn; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; RNA Polymerase II; TATA Box; TATA-Box Binding Protein
PubMed: 19267666
DOI: 10.1134/s0006297909020011 -
Nature Structural & Molecular Biology May 2023The Swi2/Snf2 family transcription regulator Modifier of Transcription 1 (Mot1) uses adenosine triphosphate (ATP) to dissociate and reallocate the TATA box-binding...
The Swi2/Snf2 family transcription regulator Modifier of Transcription 1 (Mot1) uses adenosine triphosphate (ATP) to dissociate and reallocate the TATA box-binding protein (TBP) from and between promoters. To reveal how Mot1 removes TBP from TATA box DNA, we determined cryogenic electron microscopy structures that capture different states of the remodeling reaction. The resulting molecular video reveals how Mot1 dissociates TBP in a process that, intriguingly, does not require DNA groove tracking. Instead, the motor grips DNA in the presence of ATP and swings back after ATP hydrolysis, moving TBP to a thermodynamically less stable position on DNA. Dislodged TBP is trapped by a chaperone element that blocks TBP's DNA binding site. Our results show how Swi2/Snf2 proteins can remodel protein-DNA complexes through DNA bending without processive DNA tracking and reveal mechanistic similarities to RNA gripping DEAD box helicases and RIG-I-like immune sensors.
Topics: Adenosine Triphosphatases; Transcription Factors; TATA Box; TATA-Box Binding Protein; Saccharomyces cerevisiae Proteins; DNA; Adenosine Triphosphate; TATA-Binding Protein Associated Factors
PubMed: 37106137
DOI: 10.1038/s41594-023-00966-0 -
EMBO Reports Jan 2014
Topics: Animals; Gene Expression Regulation; Humans; RNA; TATA Box
PubMed: 24363274
DOI: 10.1002/embr.201338175 -
Molecular and Cellular Biology Jan 2018A yeast system was developed that is active for transcription at both TATA-containing and TATA-less promoters. Transcription with extracts made from cells depleted of...
A yeast system was developed that is active for transcription at both TATA-containing and TATA-less promoters. Transcription with extracts made from cells depleted of TFIID subunit Taf1 demonstrated that promoters of both classes are TFIID dependent, in agreement with recent findings. TFIID depletion can be complemented by additional recombinant TATA binding protein (TBP) at only the TATA-containing promoters. In contrast, high levels of TBP did not complement Taf1 depletion and instead repressed transcription from both promoter types. We also demonstrate the importance of the TATA-like sequence found at many TATA-less promoters and describe how the presence or absence of the TATA element is likely not the only feature that distinguishes these two types of promoters.
Topics: DNA, Fungal; Gene Expression Regulation, Fungal; Mutation; Promoter Regions, Genetic; Protein Binding; RNA Polymerase II; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; TATA Box; TATA-Box Binding Protein; Transcription Factor TFIID; Transcription Initiation, Genetic
PubMed: 29038161
DOI: 10.1128/MCB.00448-17 -
Biochimica Et Biophysica Acta Apr 2016Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are...
Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.
Topics: Actins; Animals; Gene Expression Regulation; Humans; Macromolecular Substances; Promoter Regions, Genetic; Protein Binding; RNA Polymerase II; Regulatory Sequences, Nucleic Acid; Serum Response Factor; TATA Box; TATA-Binding Protein Associated Factors; TATA-Box Binding Protein; Transcription Factor TFIID; Transcription, Genetic
PubMed: 26824723
DOI: 10.1016/j.bbagrm.2016.01.005 -
Nucleic Acids Research Mar 1998The CCAAT box is one of the most common elements in eukaryotic promoters, found in the forward or reverse orientation. Among the various DNA binding proteins that... (Review)
Review
The CCAAT box is one of the most common elements in eukaryotic promoters, found in the forward or reverse orientation. Among the various DNA binding proteins that interact with this sequence, only NF-Y (CBF, HAP2/3/4/5) has been shown to absolutely require all 5 nt. Analysis of a database with 178 bona fide NF-Y binding sites in 96 unrelated promoters confirms this need and points to specific additional flanking nucleotides (C, Pu, Pu on the 5'-side and C/G, A/G, G,A/C, G on the 3'-side) required for efficient binding. The frequency of CCAAT boxes appears to be relatively higher in TATA-less promoters, particularly in the reverse ATTGG orientation. In TATA-containing promoters the CCAAT box is preferentially located in the -80/-100 region (mean position -89) and is not found nearer to the Start site than -50. In TATA-less promoters it is usually closer to the +1 signal (at -66 on average) and is sometimes present in proximity to the Cap site. The consensus and location of NF-Y binding sites parallel almost perfectly a previous general statistical study on CCAAT boxes in 502 unrelated promoters. This is an indication that NF-Y is the major, if not the sole, CCAAT box recognizing protein and that it might serve different roles in TATA-containing and TATA-less promoters.
Topics: Animals; Base Sequence; Binding Sites; CCAAT-Enhancer-Binding Proteins; Consensus Sequence; DNA; DNA-Binding Proteins; Humans; In Vitro Techniques; Promoter Regions, Genetic; Protein Binding; TATA Box
PubMed: 9469818
DOI: 10.1093/nar/26.5.1135 -
Stem Cell Research & Therapy May 2020Mesendodermal formation during early gastrulation requires the expression of lineage-specific genes, while the regulatory mechanisms during this process have not yet...
TATA box-binding protein-related factor 3 drives the mesendoderm specification of human embryonic stem cells by globally interacting with the TATA box of key mesendodermal genes.
BACKGROUND
Mesendodermal formation during early gastrulation requires the expression of lineage-specific genes, while the regulatory mechanisms during this process have not yet been fully illustrated. TATA box-binding protein (TBP) and TBP-like factors are general transcription factors responsible for the transcription initiation by recruiting the preinitiation complex to promoter regions. However, the role of TBP family members in the regulation of mesendodermal specification remains largely unknown.
METHODS
We used an in vitro mesendodermal differentiation system of human embryonic stem cells (hESCs), combining with the microarray and quantitative polymerase chain reaction (qRT-PCR) analysis, loss of function and gain of function to determine the function of the TBP family member TBP-related factor 3 (TRF3) during mesendodermal differentiation of hESCs. The chromatin immunoprecipitation (ChIP) and biochemistry analysis were used to determine the binding of TRF3 to the promoter region of key mesendodermal genes.
RESULTS
The mesendodermal differentiation of hESCs was confirmed by the microarray gene expression profile, qRT-PCR, and immunocytochemical staining. The expression of TRF3 mRNA was enhanced during mesendodermal differentiation of hESCs. The TRF3 deficiency did not affect the pluripotent marker expression, alkaline phosphatase activity, and cell cycle distribution of undifferentiated hESCs or the expression of early neuroectodermal genes during neuroectodermal differentiation. During the mesendodermal differentiation, the expression of pluripotency markers decreased in both wild-type and TRF3 knockout (TRF3) cells, while the TRF3 deficiency crippled the expression of the mesendodermal markers. The reintroduction of TRF3 into the TRF3 hESCs rescued inhibited mesendodermal differentiation. Mechanistically, the TRF3 binding profile was significantly shifted to the mesendodermal specification during mesendodermal differentiation of hESCs based on the ChIP-seq data. Moreover, ChIP and ChIP-qPCR analysis showed that TRF3 was enriched at core promoter regions of mesendodermal developmental genes, EOMESODERMIN, BRACHYURY, mix paired-like homeobox, and GOOSECOID homeobox, during mesendodermal differentiation of hESCs.
CONCLUSIONS
These results reveal that the TBP family member TRF3 is dispensable in the undifferentiated hESCs and the early neuroectodermal differentiation. However, it directs mesendodermal lineage commitment of hESCs via specifically promoting the transcription of key mesendodermal transcription factors. These findings provide new insights into the function and mechanisms of the TBP family member in hESC early lineage specification.
Topics: Carrier Proteins; Cell Differentiation; Gene Expression Regulation, Developmental; Human Embryonic Stem Cells; Humans; Nuclear Proteins; TATA Box; TATA Box Binding Protein-Like Proteins
PubMed: 32448362
DOI: 10.1186/s13287-020-01711-w -
Genomics Dec 2014The TATA box is the core sequence of the promoter and the binding site of many transcription factors. Based on the presence or absence of TATA box, genes can be defined...
The TATA box is the core sequence of the promoter and the binding site of many transcription factors. Based on the presence or absence of TATA box, genes can be defined as TATA-containing or TATA-less genes. Many important stress-response functions and highly variable expression patterns are found to be correlated with the TATA box. However, until now, the relationships and differences between TATA-containing and TATA-less genes remain unclear. In this study, based on the transcriptional profiling of the Saccharomyces cerevisiae genome, the perturbation sensitivity (PS) network is constructed. The topological and biological properties are used to investigate differences between TATA-containing and TATA-less genes. Significant differences are found in all topological properties and most of the biological properties. Notably, the TF number, determined mathematically by the number of transcription factors regulating a gene, demonstrates the highest discrimination between TATA-containing and TATA-less genes when all properties are estimated by the F-score.
Topics: Gene Regulatory Networks; Genes, Fungal; Saccharomyces cerevisiae; TATA Box
PubMed: 25451177
DOI: 10.1016/j.ygeno.2014.10.005