Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human beta-globin locus control region (LCR) is responsible for forming an active chromatin structure extending over the 100-kb locus, allowing expression of the beta-globin gene family. The LCR consists of four erythroid-cell-specific DNase I hypersensitive sites (HS1 to -4). DNase I hypersensitive sites are thought to represent nucleosome-free regions of DNA which are bound by trans-acting factors. Of the four hypersensitive sites only HS2 acts as a transcriptional enhancer. In this study, we examine the binding of an erythroid protein to its site within HS2 in chromatin in vitro. NF-E2 is a transcriptional activator consisting of two subunits, the hematopoietic cell-specific p45 and the ubiquitous DNA-binding subunit, p18. NF-E2 binds two tandem AP1-like sites in HS2 which form the core of its enhancer activity. In this study, we show that when bound to in vitro-reconstituted chromatin, NF-E2 forms a DNase I hypersensitive site at HS2 similar to the site observed in vivo. Moreover, NF-E2 binding in vitro results in a disruption of nucleosome structure which can be detected 200 bp away. Although NF-E2 can disrupt nucleosomes when added to preformed chromatin, the disruption is more pronounced when NF-E2 is added to DNA prior to chromatin assembly. Interestingly, the hematopoietic cell-specific subunit, p45, is necessary for binding to chromatin but not to naked DNA. Interaction of NF-E2 with its site in chromatin-reconstituted HS2 allows a second erythroid factor, GATA-1, to bind its nearby sites. Lastly, nucleosome disruption by NF-E2 is an ATP-dependent process, suggesting the involvement of energy-dependent nucleosome remodeling factors.
 ...
PMID:NF-E2 disrupts chromatin structure at human beta-globin locus control region hypersensitive site 2 in vitro. 881 76

Homodimeric DNA-binding proteins with relaxed half-site spacing requirements for their DNA targets have been described. As an example, the yeast transcriptional activator Gcn4p binds in vitro equally well to the AP1 site (5'A4T3G2A1C0T1'C2'A3'T4'3') and the ATF/CREB site (5'A4T3G2A1C0G0'T1'C2'A3'T4'3'), which have identical but differently spaced half-site blocks. We describe a novel feature for the bZip class of DNA-binding proteins. The N-14 mutant of a Gcn4p-derived bZip peptide shows a diametrically opposed base-pair recognition specificity depending on the half-site spacing of its DNA target: on pseudo-palindromic, AP1 site-like binding sites, guanine is required in position 2 for proper binding; in contrast, on palindromic, ATF/CREB site-like targets, position 2 must be cytosine to prevent a loss of binding. Modeling studies suggest that the different base-pair requirements on differently spaced DNA targets are due to minimal alterations of the distances between the relevant atoms of the N-14 side-chain and the corresponding target groups on the DNA. Although the N-14 peptide does not have a natural counterpart, its behavior hints at the possibility that dual binding modi dependent on half-site spacing may occur also for natural homodimeric DNA-binding proteins.
 ...
PMID:A novel feature of DNA recognition: a mutant Gcn4p bZip peptide with dual DNA binding specificities dependent of half-site spacing. 1004 75

Development of the cauliflower phenotype in Arabidopsis thaliana requires mutations at both the CAULIFLOWER and APETALA1 loci. BoAP1 is the Brassica oleracea orthologue to the Arabidopsis AP1 gene, and is present in two copies in Brassica genomes. The BoAP1-A gene appears to encode a full-length protein, but BoAP1-B alleles in B. oleracea contain insertions that lead to premature translation termination. The BoAP1-B allele found in most B. oleracea subspecies, including B. oleracea ssp. botrytis (domesticated cauliflower) contains a 9 bp insertion in exon 4. This insertion leads to the formation of an in-frame translation termination codon, and these alleles can encode a protein that is truncated at the K domain of this MADS-box transcriptional activator. The allele in B. oleracea ssp. oleracea (wild cabbage) lacks this insertion and instead contains a downstream 4 bp frameshift mutation resulting in the formation of a nonsense mutation. The structure of the BoAP1-B alleles suggests that they are impaired in their ability to perform their floral meristem identity function. These mutations, in conjunction with mutations at the BoCAULIFLOWER (BoCAL) locus, may be associated with the evolution of domesticated cauliflower.
 ...
PMID:Duplication of the Brassica oleracea APETALA1 floral homeotic gene and the evolution of domesticated cauliflower. 1054 96

Noradrenergic neuronal identity and differentiation are controlled by cascades of transcription factors acting downstream of BMP4, including the basic helix-loop-helix DNA binding protein HAND2 and the homeodomain factor Phox2a. Dopamine-beta-hydroxylase (DBH) is the penultimate enzyme required for synthesis of norepinephrine and is thus a noradrenergic cell type-specific marker. We have examined the interaction of HAND2 and Phox2a at the DBH promoter. Using transient transfection of P19 or NT-2 cells, HAND2 is shown to synergistically enhance Phox2a-driven transcriptional activity at the DBH promoter, an effect that is enhanced by cAMP. While mutation of the Phox2a homeodomain binding sites HD1, HD2, and HD3 results in the loss of HAND2/Phox2a transactivation of DBH, it is the interaction of HAND2/Phox2a at the CRE/AP1-HD1/2 domains in the DBH enhancer that are required for synergistic activation by HAND2. We find that HAND2 functions as a transcriptional activator without directly binding to E-box sequences in the DBH promoter, suggesting that HAND2-mediated DBH activity occurs by protein-protein interactions with other transcriptional regulators. Although we were unable to detect interaction of HAND2 and Phox2a in IP/Western blots, HAND2 synergistic activation of DBH is blocked by E1A, suggesting that HAND2 interacts with CBP (cAMP response element binding protein) in this transcriptional complex. In the presence of the putative HAND2 dimerization partner, E12, synergistic activation of DBH transcription is titrated away, suggesting that HAND2 does not functionally dimerize with E12 in the DBH transcription complex. Our data suggest that HAND2 regulates cell type-specific expression of norepinephrine in concert with Phox2a by a novel mechanism.
 ...
PMID:HAND2 synergistically enhances transcription of dopamine-beta-hydroxylase in the presence of Phox2a. 1451 28

The marine gamma-Proteobacterium Alcanivorax borkumensis is highly specialized in the assimilation of aliphatic hydrocarbons, and makes up a large part of the biomass in oil-polluted marine environments. In addition to the previously identified alkane hydroxylase AlkB1, a second alkane hydroxylase (AlkB2) showing 65% identity to the Pseudomonas aeruginosa AlkB2 alkane hydroxylase was identified. Unlike alkB1, alkB2 is not flanked by genes involved in alkane metabolism. Heterologous expression of the A. borkumensis AP1 alkB1 and alkB2 genes showed that they encode functional alkane hydroxylases with substrate ranges similar to those of their P. putida and P. aeruginosa homologues. The transcription initiation sites and levels of the alkB1, alkB2 and alkS mRNA transcripts were determined. Expression of both alkB1 and alkB2 was induced by alkanes, but transcripts corresponding to alkB1 were much more abundant than those of alkB2. An inverted repeat similar to the binding site for the P. putida GPo1 transcriptional activator AlkS was present upstream of the promoters for alkB1 and alkB2, although that of alkB2 was less well conserved, and only the transcriptional fusion of promoter PalkB1 to the reporter gene lacZ efficiently responded to n-octane. Contrary to what has been found for the P. putida GPo1 alkane degradation pathway, expression of the A. borkumensis AP1 alkS gene was not induced by alkanes, and an AlkS binding site was not present upstream of the promoter for alkS. This indicates that, in spite of the clear similarities, the A. borkumensis alk-genes are regulated by a strategy different from that of the P. putida GPo1 alk genes.
 ...
PMID:Characterization of two alkane hydroxylase genes from the marine hydrocarbonoclastic bacterium Alcanivorax borkumensis. 1487 Dec 10

TonEBP [TonE (tonicity-responsive enhancer)-binding protein] is a transcriptional activator of the Rel family like NF-kappaB (nuclear factor kappaB) and NFAT (nuclear factor of activated T-cells). TonEBP plays a key role in the protection of cells in the kidney medulla from the deleterious effects of hyperosmolality. This is achieved by enhancing expression of HSP70 (heat-shock protein 70) and other genes whose products drive cellular accumulation of organic osmolytes. TonEBP is stimulated by ambient hypertonicity via multiple pathways that regulate nuclear translocation and transactivation. In the present paper, we report that TonEBP is associated in vivo with RHA (RNA helicase A). The N- and C-termini of RHA bound the E'F loop of the DNA-binding domain of TonEBP. The interaction was not affected by DNA binding or dimerization of TonEBP. Overexpression of RHA inhibited the activity of TonEBP; however, catalytic activity of RHA was dispensable for the inhibition. When the ambient tonicity was raised, the TonEBP-RHA interaction decreased, suggesting that dissociation of RHA is a pathway to stimulate TonEBP. We conclude that the E'F loop of TonEBP interacts with RHA like NFAT and NF-kappaB interact with AP1 (activator protein 1) and the high-mobility group protein HMG-I(Y) respectively. While RHA interacts with and stimulates other transcription factors such as CREB (cAMP-response-element-binding protein), NF-kappaB and mineralocorticoid receptor, it inhibits TonEBP.
 ...
PMID:TonEBP is inhibited by RNA helicase A via interaction involving the E'F loop. 1617 19

Although in vitro studies of embryonic stem cells have identified polycomb repressor complexes (PRCs) as key regulators of differentiation, it remains unclear as to how PRC-mediated mechanisms control fates of multipotent progenitors in developing tissues. Here, we show that an essential PRC component, Ezh2, is expressed in epidermal progenitors but diminishes concomitant with embryonic differentiation and with postnatal decline in proliferative activity. We show that Ezh2 controls proliferative potential of basal progenitors by repressing the Ink4A-Ink4B locus and tempers the developmental rate of differentiation by preventing premature recruitment of AP1 transcriptional activator to the structural genes that are required for epidermal differentiation. Together, our studies reveal that PRCs control epigenetic modifications temporally and spatially in tissue-restricted stem cells. They maintain their proliferative potential and globally repressing undesirable differentiation programs while selectively establishing a specific terminal differentiation program in a stepwise fashion.
 ...
PMID:Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. 1930 40

ZFPs (Zinc Finger Proteins) play important roles in various cellular functions, including transcriptional activation, transcriptional repression, cell proliferation, and development. C(2)H(2) (Cys-Cys-His-His motif) ZFPs are the most abundant proteins among the founding members of the ZFP super family in eukaryotes. In this study, we isolate a novel C(2)H(2) ZNF (Zinc Finger) gene ZNFD. It contains an ORF (Open Reading Frame) with a length of 990 bp, encoding 329 amino acids. The predicted protein contains a C(2)H(2) zinc finger. RT-PCR analysis in 18 human adult tissues indicated that it was expressed in five human adult tissues. Green fluorescence protein localization analysis showed that human ZNFD was located in the nucleus of Hela cells. Overexpression of ZNFD in the COS7 cells activates the transcriptional activities of AP1(PMA) (Activator of protein 1, that responds specifically to phorbol ester). Together the data indicate that ZNFD is probably a new type of C(2)H(2) ZFP and the ZNFD protein may act as a transcriptional activator in PKC (protein kinase C) signal pathway to mediate cellular functions.
 ...
PMID:Isolation and characterization of a novel zinc finger gene, ZNFD, activating AP1(PMA) transcriptional activities. 2016 41

Cotton fibers, as natural fibers, are widely used in the textile industry in the world. In order to find genes involved in fiber development, a cDNA (designated as GhMADS11) encoding a novel MADS protein with 151 amino acid residues was isolated from cotton fiber cDNA library. The deduced protein shares high similarity with Arabidopsis AP1 and AGL8 in MADS domain. However, the GhMADS11 protein (being absent of the partial K-domain and normal C-terminus) is shorter than AP1 and AGL8 by the reason of gene frameshift mutation during evolution. The experimental results revealed that GhMADS11 was not a transcriptional activator, and it did not form homodimer. GhMADS11 transcripts were specifically accumulated in elongating fibers, but no or very low signals of its expression were detected in other tissues of cotton. Overexpression of GhMADS11 in fission yeast promotes atypical cell elongation by 1.4-2.0-fold. Furthermore, morphological analysis indicated that the transformed cells expressing GhMADS11m, a MIKC-type derivative of GhMADS11 by the site-directed mutation, displayed the same phenotype as that of the transformed cells with GhMADS11. The concurrence of these data sets suggested that GhMADS11 protein may function in fiber cell elongation, and its MADS domain and partial K-domain are sufficient for this function.
 ...
PMID:A cotton gene encoding novel MADS-box protein is preferentially expressed in fibers and functions in cell elongation. 2173 55


<< Previous 1 2