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PubMed1998

Regulation of iron metabolism in the sanguivore lamprey Lampetra fluviatilis--molecular cloning of two ferritin subunits and two iron-regulatory proteins (IRP) reveals evolutionary conservation of the iron-regulatory element (IRE)/IRP regulatory system.

Two ferritin cDNAs were cloned from the liver and spinal cord of the sanguivore lamprey Lampetra fluviatilis, an extant representative of the ancient agnathan (jawless) stage in vertebrate evolution. The deduced proteins of 20.2 kDa (H-subunit) and 20.1 kDa (M-subunit) display 73% sequence identity, and both contain the ferroxidase center characteristic of animal H-ferritin. A highly conserved iron-responsive element (IRE) was identified in the 5' untranslated region of lamprey H-ferritin. Lamprey ferritin IRE forms a specific complex with crude lamprey and rat liver extracts, and with recombinant human iron-regulatory protein (IRP-1) in an electrophoretic mobility shift assay. Furthermore, lamprey ferritin IRE competes with labeled human ferritin IRE for binding to IRP in lamprey and mammalian extracts. Two liver cDNA sequences encoding 323 residues and 101 residues of two genetically distinct lamprey IRP were amplified by PCR. Lamprey IRP-1 and IRP-2, which are 72% identical, display about 74% sequence identity to their presumed homologues in mammals. Northern blot analysis shows that two IRP transcripts of 3.6 kb and 5.8 kb are expressed in lamprey liver. Given the ancient lineage of lampreys, the results indicate that the IRE/IRP regulatory system has remained highly conserved during the evolution of vertebrates.

Amino Acid Sequence↗

PubMed1998

Sp1 and Sp3 transactivate the human lipoprotein lipase gene promoter through binding to a CT element: synergy with the sterol regulatory element binding protein and reduced transactivation of a naturally occurring promoter variant.

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and energy metabolism and, therefore, regulation of its expression could have an important bearing on these processes. We have identified an evolutionarily conserved 5'-CCTCCCCCC-3' motif (from -91 to -83, CT element) in the human LPL gene promoter, deletion or mutation of which caused approximately 70-80% decrease in promoter activity. We found that Sp1 and Sp3 in THP-1 nuclear protein extracts bind specifically to this element. Co-transfection with Sp1 and Sp3 expression plasmids transactivated the LPL promoter via the CT element in Drosophila SL2 cells devoid of Sp proteins. Sp3 moderately repressed Sp1-mediated LPL promoter activation when both were co-expressed in SL2 cells. Furthermore, co-expression of an active sterol regulatory element binding protein (SREBP-1), with Sp1, but not with Sp3, synergistically activated the LPL promoter in SL2 cells. We previously reported a naturally occurring T-->G substitution at position -93 of the human LPL promoter which reduces promoter activity by 40-50% in transient transfection assays. In this study, we showed that this substitution results in reduced binding affinity to Sp1/Sp3 and in diminished transactivation by Sp1/Sp3 alone and by the synergistic action of Spl and SREBP-1 In conclusion, recruitment of Sp1/Sp3 by the CT element may play an important role in expression of the human lipoprotein lipase gene. Synergistic transcriptional activation by Sp1 and SREBP-1 may provide a mechanism for cross-talk between cholesterol and triglyceride metabolic pathways.

Base Sequence↗

PubMed1992

A transcriptional regulatory element of the gene encoding the 67,000-M(r) form of human glutamate decarboxylase is similar to a Drosophila regulatory element.

We have isolated the 5' flanking DNA sequences of the human gene encoding the 67,000-M(r) form of glutamate decarboxylase (GAD67), the gamma-aminobutyric acid synthetic enzyme. Transcription begins at a single promoter (P1) in adult brain but at two tandem promoters, P1 and P2, in fetal brain. P1, which is 3' to P2, resembles the promoter regions of many constitutively expressed genes, whereas P2 resembles a tissue-specific promoter. P1 contains a 10-base sequence (dec-1) that closely matches the element I cis-regulatory sequence identified in the promoter region of Drosophila 3,4-dihydroxyphenylalanine decarboxylase. Gel shift and transient expression assays demonstrate that the dec-1 sequence plays a role in the transcription of the human GAD67 gene.

Animals↗

PubMed1992

Characterization of the hepatitis B virus X- and nucleocapsid gene transcriptional regulatory elements.

The regulatory DNA sequence elements that control the expression of the hepatitis B virus X- and nucleocapsid genes in the differentiated human hepatoma cell lines, Huh7, Hep3B, PLC/PRF/5, and HepG2, the dedifferentiated human hepatoma cell line, HepG2.1, and the human cervical carcinoma cell line, HeLa S3, were analyzed using transient transfection assays. In this system, the hepatitis B virus enhancer I located between coordinates 1071 (-239) and 1238 (-72) increases transcription from the X-gene promoter located between coordinates 1239 (-71) and 1376 (+67) more than 30-fold in the differentiated hepatoma and the HeLa S3 cell lines. In the dedifferentiated hepatoma cell line, HepG2.1, the enhancer I sequence increases the level of transcription from the X-gene promoter approximately 10-fold. The enhancer I subregion between coordinates 1117 (-193) and 1204 (-106) appears to be important for enhancer function only in the differentiated hepatoma cell lines, whereas the enhancer I subregion between coordinates 1222 (-88) and 1238 (-72) is required for enhancer activity in each of the cell lines examined. In all of the cell lines, the X-gene minimal promoter element was within a 138-nucleotide sequence located between coordinates 1239 (-71) and 1376 (+67). The enhancer I sequence increases transcription from the nucleocapsid promoter approximately 3- to 10-fold in the Huh7, Hep3B, PLC/PRF/5, and HeLa S3 cell lines, whereas it had little influence on the level of transcription from this promoter in HepG2 and HepG2.1 cells. The minimal nucleocapsid promoter element was within a 105 nucleotide sequence located between coordinates 1700 (-85) and 1804 (+20). This indicates that the levels of transcription from the X- and nucleocapsid gene promoters are determined in a cell-type-specific manner, in part, by the hepatitis B virus enhancer I and the corresponding minimal promoter sequence.

Base Sequence↗

PubMed2002

Estrogen activates the high-density lipoprotein receptor gene via binding to estrogen response elements and interaction with sterol regulatory element binding protein-1A.

The effects of E2 on the high-density lipoprotein receptor (HDL-R) scavenger receptor class B type I (SR-BI) gene were examined. Four putative estrogen response element half-site motifs (ERE(1/2)) (-2176, -1726, -1622, and -1211, designated ERE(1/2)-1, 2, 3, and 4, respectively) were identified in the HDL-R SR-BI promoter. Transfection studies and mutation analysis demonstrated that E2 significantly increased HDL-R SR-BI promoter activity and that mutating ERE(1/2)-1, 2, and 4 resulted in a loss of E2 responsiveness. Both ER alpha and ER beta formed specific complexes with ERE(1/2)-1, 2, and 4 but did not bind ERE(1/2)-3 in vitro. Interestingly, ERE(1/2)-3 was the motif shown not to be important for E2-activation of the HDL-R SR-BI promoter in the mutational analysis studies. The influence of SREBP-1a (sterol regulatory element binding protein-1a) on E2 regulation of the HDL-R SR-BI gene was also examined. SREBP-1a was able to bind directly to the ERE(1/2) motifs and enhanced ER binding when both ER subtypes were present. ER alpha and beta also bound to a sterol response element motif, but they did not enhance SREBP-1a binding. Cotransfection studies demonstrated that the presence of the three factors, ER alpha, ER beta, and SREBP-1a, enhanced the overall luciferase activity produced from the HDL-R SR-BI promoter construct in the presence of only one of the factors. Interaction of SREBP-1a with both ERs was demonstrated using a mammalian two-hybrid assay. The data confirmed that E2 through the ERs can positively regulate the HDL-R SR-BI through binding and activation of three ERE(1/2) motifs and identified SREBP-1a as a potential coactivator of the E2-ER-dependent effects on the HDL-R SR-BI gene.

Blotting, Western↗

PubMed2003

The new RENT family of repetitive elements in Nicotiana species harbors gene regulatory elements related to the tCUP cryptic promoter.

The tCUP cryptic constitutive promoter was discovered in the tobacco genome by T-DNA (transfer DNA) tagging with a promoterless GUS-nos gene. Here, we show that the portion of the tCUP sequence containing a variety of cryptic gene regulatory elements is related to a new family of moderately repetitive sequences (10(2) copies), the RENT (repetitive element from Nicotiana tabacum) family. The RENT family is found only in certain Nicotiana species. Five RENT elements were cloned and sequenced. The RENT elements are a minimum of 5 kb in length and share 80-90% sequence similarity throughout their length. The 5' termini are the same in the isolated RENT family members and are characterized by a conserved border sequence (TGTTGA(T or C)ACCCAATTTT(T or C)). The 3' ends of RENT sequence similarity vary in location and sequence. The tCUP cryptic promoter originated from a unique truncated RENT element that interrupts a phytochelatin synthase-like gene that may have undergone rearrangements prior to or resulting from T-DNA insertion. No evidence was found for expressed coding regions within the RENT elements; however, like the cryptic gene regulatory elements within the tCUP sequence, the isolated RENT elements possess promoter activity and translational enhancer activity.

Base Sequence↗

PubMed1998

Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins.

Activation of genes containing SRE-1 (sterol regulatory element 1) sequences is known to be under the regulation of sterols through modulation of the proteolytic maturation of SREBPs (SRE-1-binding proteins). Previous work has demonstrated SREBP-mediated transcriptional activation of genes encoding enzymes of sterol and fatty acid biosynthesis. Because synthesis of both sterols and C18 fatty acids are required for cell growth, in the absence of exogenous supplements of these lipids, we examined the hypothesis that fatty acid can also be regulatory in SREBP maturation. Our data indicate that C18 fatty acids can potentiate the biological activities of a typical, regulatory sterol: 25-hydroxycholesterol. Inhibition of C18 fatty acid synthesis in cells cultured in serum-free medium renders them resistant to killing by 25-hydroxycholesterol. Repression of expression of reporter constructs driven by promoters bearing SRE-1 element(s) by 25-hydroxycholesterol is increased by C18 fatty acid supplementation. C18 fatty acids also increase the inhibitory effect of 25-hydroxycholesterol on proteolytic maturation and nuclear localization of SREBPs. Furthermore, we also show that C18 fatty acid supplementation can enhance the inhibitory effect of 25-hydroxycholesterol on sterol and fatty acid biosynthesis. These results demonstrate that maximal down-regulation of SREBP maturation and the consequent repression of SRE-1 promoters occurs in response to both a regulatory sterol and fatty acid.

Alkynes↗

PubMed2006

TFBScluster web server for the identification of mammalian composite regulatory elements.

Identification of transcriptional regulatory elements represents a critical step in our ability to reconstruct transcriptional regulatory networks from gene expression profiling datasets. To facilitate computational identification of candidate gene regulatory elements from whole genome sequences, we have developed the TFBScluster web server that integrates several tools for the genome-wide identification and subsequent characterization of transcription factor binding site clusters that are conserved in multiple mammalian species. Either the human or mouse genomes can be used as the reference sequence with direct links from the search results to the ENSEMBL and UCSC genome browsers. Moreover, TFBScluster provides seamless integration of transcription factor binding site searches with genome annotation and gene expression profiling data, to allow prioritising computational predictions for subsequent experimental validation. TFBScluster is publicly available at http://hscl.cimr.cam.ac.uk/TFBScluster_genome_portal.html.

Animals↗

PubMed1991

A binding site for the cyclic adenosine 3',5'-monophosphate-response element-binding protein as a regulatory element in the grp78 promoter.

The 78-kDa glucose-regulated protein (GRP78) is ubiquitously expressed in many cell types. Its promoter contains multiple protein-binding sites and functional elements. In this study we examined a high affinity protein-binding site spanning bp -198 to -180 of the rat grp78 promoter, using nuclear extracts from both B-lymphoid and HeLa cells. This region contains a sequence TGACGTGA which, with the exception of one base, is identical to the cAMP-response element (CRE). Site-directed mutagenesis reveals that this sequence functions as a major basal level regulatory element in hamster fibroblast cells and is also necessary to maintain high promoter activity under stress-induced conditions. By gel mobility shift analysis, we detect two specific protein complexes. The major specific complex I, while immunologically distinct from the 42-kDa CRE-binding protein (CREB), binds most strongly to the grp site, but also exhibits affinity for the CRE consensus sequence. As such, complex I may consist of other members of the CREB/activating transcription factor protein family. The minor specific complex II consists of CREB or a protein antigenically related to it. A nonspecific complex III consists of the Ku autoantigen, an abundant 70- to 80-kDa protein complex in HeLa nuclear extracts. By cotransfection experiments, we demonstrate that in F9 teratocarcinoma cells, the grp78 promoter can be transactivated by the phosphorylated CREB or when the CREB-transfected cells are treated with the calcium ionophore A23187. The differential regulation of the grp78 gene by cAMP in specific cell types and tissues is discussed.

B-Lymphocytes↗

PubMed2005

Multiple cis-regulatory elements and the yeast sulphur regulatory network are required for the regulation of the yeast glutathione transporter, Hgt1p.

HGT1 encodes a high-affinity glutathione transporter in the yeast Saccharomyces cerevisiae that is induced under sulphur limitation. The present work demonstrates that repression by organic sulphur sources is under the control of the classic sulphur regulatory network, as seen by the absence of expression in a met4delta background. Cysteine appeared to be the principal regulatory molecule, since elevated levels were seen in str4delta strains (deficient in cysteine biosynthesis) that could be repressed by elevated levels of cysteine, but not by methionine or glutathione. Investigations into cis-regulatory elements revealed that the previously described motif, a 9-bp cis element, CCGCCACAC, located at the -356 to -364 region of the promoter could in fact be refined to a 7-bp CGCCACA motif that is also repeated at -333 to -340. The second copy of this motif was essential for activity, since mutations in the core region of the second copy completely abolished activity and regulation by sulphur sources. Activity, but not regulation, could be restored by reintroducing an additional copy upstream of the first copy. A third region, GCCGTCTGCAAGGCA, conserved in the HGT1 promoters of the different Saccharomyces spp, was observed at -300 to -285 but, while mutations in this region did not lead to any loss in repression, the basal and induced levels were significantly increased. In contrast to a previous report, no evidence was found for regulation by the VDE endonuclease. The strong repression at the transport level by glutathione seen in strains overexpressing HGT1 was due to a glutathione-dependent toxicity in these cells.

Base Sequence↗

PubMed2001

Characterization of the mouse metal-regulatory-element-binding proteins, metal element protein-1 and metal regulatory transcription factor-1.

Metal activation of metallothionein gene transcription depends mainly on the presence of regulatory DNA sequences termed metal-regulatory elements (MREs) and involves MRE-binding transcription factor-1 (MTF-1) interacting with the MREs in a Zn(2+)-dependent manner. We previously identified and characterized a nuclear protein, termed metal element protein-1 (MEP-1), specifically binding with high affinity to MRE elements. The precise relationship between MTF-1 and MEP-1 was unclear, and to determine whether MEP-1 and MTF-1 were distinct protein species, we performed DNA binding analyses to characterize the binding properties of both proteins. Electrophoretic mobility-shift assays showed that MTF-1, produced in COS cells, produces a slower-migrating band compared with that obtained with purified MEP-1. Using an anti-MTF-1 antibody, we showed that both the MTF-1-MRE and the MEP-1-MRE complexes are supershifted by an anti-MTF-1 antibody, thus demonstrating that MEP-1 is antigenically related to MTF-1. RNase protection analyses carried out with RNA prepared from different tissues and cell lines failed to reveal the presence of MTF-1 splicing variants. This indicates that MEP-1 may be a proteolytic fragment of MTF-1. MTF-1 DNA-binding activity was rapidly activated in vivo by Zn(2+) ions but not by Cd(2+), UV irradiation or PMA, and occurred on ice as well as at 21 degrees C. In control and Zn(2+)-treated cell extracts, DNA-binding activity was not enhanced in vitro following the addition of exogenous Zn(2+) or a preincubation at 37 degrees C. However, recombinant MTF-1 produced in vitro required Zn(2+) activation for DNA binding. Interestingly, treatment of nuclear extracts with calf intestine phosphatase completely abrogated MTF-1 DNA-binding activity, thus suggesting that phosphorylation is involved in the regulation of MTF-1 activity.

Animals↗

PubMed2006

AGRIS and AtRegNet. a platform to link cis-regulatory elements and transcription factors into regulatory networks.

Gene regulatory pathways converge at the level of transcription, where interactions among regulatory genes and between regulators and target genes result in the establishment of spatiotemporal patterns of gene expression. The growing identification of direct target genes for key transcription factors (TFs) through traditional and high-throughput experimental approaches has facilitated the elucidation of regulatory networks at the genome level. To integrate this information into a Web-based knowledgebase, we have developed the Arabidopsis Gene Regulatory Information Server (AGRIS). AGRIS, which contains all Arabidopsis (Arabidopsis thaliana) promoter sequences, TFs, and their target genes and functions, provides the scientific community with a platform to establish regulatory networks. AGRIS currently houses three linked databases: AtcisDB (Arabidopsis thaliana cis-regulatory database), AtTFDB (Arabidopsis thaliana transcription factor database), and AtRegNet (Arabidopsis thaliana regulatory network). AtTFDB contains 1,690 Arabidopsis TFs and their sequences (protein and DNA) grouped into 50 (October 2005) families with information on available mutants in the corresponding genes. AtcisDB consists of 25,806 (September 2005) promoter sequences of annotated Arabidopsis genes with a description of putative cis-regulatory elements. AtRegNet links, in direct interactions, several hundred genes with the TFs that control their expression. The current release of AtRegNet contains a total of 187 (September 2005) direct targets for 66 TFs. AGRIS can be accessed at http://Arabidopsis.med.ohio-state.edu.

Arabidopsis↗

PubMed1999

Distinct export pathway utilized by the hepatitis B virus posttranscriptional regulatory element.

The posttranscriptional regulatory element (PRE) of hepatitis B virus is an RNA element important for the export of viral mRNA from the nucleus to the cytoplasm. The cellular export pathway utilized by the PRE is controversial. We present data showing that PRE-dependent export is blocked by vesicular stomatitis virus matrix protein, an inhibitor of all cellular RNA export other than tRNA export. It is also blocked by a mutated form of Ran-binding protein 1, which blocks export mediated by the human immunodeficiency virus Rev and Rev-response element (RRE) but not export mediated by the simian retrovirus constitutive transport element (CTE). On the other hand, PRE-dependent export is not blocked by either TAgRex or leptomycin B, two agents that prevent Rev/RRE-mediated export. Therefore, PRE appears to utilize an export pathway different from that of Rev/RRE or CTE.

Biological Transport↗

PubMed2005

Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver.

In mammals, the regulation of hepatic metabolism plays a key role in whole body energy balance, since the liver is the major site of carbohydrate metabolism (glycolysis and glycogen synthesis) and triglyceride synthesis (lipogenesis). Lipogenesis is regulated through the acute control of key enzyme activities by means of allosteric and covalent modifications. Moreover, the synthesis of most glycolytic and lipogenic enzymes is regulated in response to dietary status, in which glucose, in particular, is a crucial energy nutrient. This latter response occurs in large part through transcriptional regulation of genes encoding glycolytic and lipogenic enzymes. In the past few years, recent advances have been made in understanding the transcriptional regulation of hepatic glycolytic and lipogenic genes by insulin and glucose. Although insulin is a major regulator of hepatic lipogenesis, there is increasing evidence that glucose also contributes to the coordinated regulation of carbohydrate and lipid metabolism in liver. Here, we review the respective roles of the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) in mediating the effect of insulin on hepatic gene expression, and the role of carbohydrate responsive element binding protein (ChREBP) in regulating gene transcription by glucose.

Animals↗

PubMed1995

Modulation of APRT transcription by altering spacing between cis-regulatory elements.

Three regulatory regions on the promoter of CHO adenine phosphoribosyltransferase gene (APRT) were identified. Spacing constraints between these regions were analyzed. With normal spacing, region II (-33 to +19), which separates regions I (-101 to -53) and III (+56 to +85), is critical for APRT transcription. However, when regions I and III are artificially placed in proximity to each other (region II deleted), they are able to drive transcription as efficiently as the wild-type APRT promoter. Neither region I nor III alone is sufficient for efficient transcription. As the spacing between the two regions increases, the transcription decreases. Region I may activate transcription in two ways: through a stringent sequence-specific manner (as in the transcription mediated by regions I and III) and through a manner with relaxed requirement for sequence specificity (as in the transcription from the wild-type APRT promoter).

Adenine Phosphoribosyltransferase↗

PubMed1992

Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression.

The observation that vitamin D-mediated enhancement of osteocalcin (OC) gene expression is dependent on and reciprocally related to the level of basal gene expression suggests that an interaction of the vitamin D responsive element (VDRE) with basal regulatory elements of the OC gene promoter contributes to both basal and vitamin D-enhanced transcription. Protein-DNA interactions at the VDRE of the rat OC gene (nucleotides -466 to -437) are reflected by direct sequence-specific and antibody-sensitive binding of the endogenous vitamin D receptor present in ROS 17/2.8 osteosarcoma nuclear protein extracts. In addition, a vitamin D-responsive increase in OC gene transcription is accompanied by enhanced non-vitamin D receptor-mediated protein-DNA interactions in the "TATA" box region (nucleotides -44 to +23), which also contains a potential glucocorticoid responsive element. Evidence for proximity of the VDRE with the basal regulatory elements is provided by two features of nuclear architecture. (i) Nuclear matrix attachment elements in the rat OC gene promoter that bind nuclear matrix proteins with sequence specificity may impose structural constraints on promoter conformation. (ii) Limited micrococcal nuclease digestion and Southern blot analysis indicate that three nucleosomes can be accommodated in the sequence spanning the OC gene VDRE, the OC/CCAAT box (nucleotides -99 to -76), and the TATA/glucocorticoid responsive element, and thereby the potential distance between the VDRE and the basal regulatory elements can be reduced. A model is presented for the contribution of both the VDRE and proximal promoter elements to the enhancement of OC gene transcription in response to vitamin D. The vitamin D receptor plus accessory proteins may function cooperatively with basal regulatory factors to modulate the extent to which the OC gene is transcribed.

Animals↗

PubMed2005

Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2.

Caspases play important roles in apoptotic cell death and in some other functions, such as cytokine maturation, inflammation, or differentiation. We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), proteins that mediate the transcriptional activation of genes involved in cholesterol, triacylglycerol, and fatty acid synthesis. Exposure of several human cell lines to statins, lipid-lowering drugs that drive SREBP proteolytic activation, induced the CASP-2 gene to an extent similar to that for known targets of SREBP proteins. Adenoviral vector-mediated transfer of active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content. These rises in lipids were strongly impaired following small interfering RNA-mediated silencing of the CASP-2 gene. Taken together, our results identify the human CASP-2 gene as a member of the SREBP-responsive gene battery that senses lipid levels in cells and raise the possibility that caspase-2 participates in the control of cholesterol and triacylglycerol levels.

5' Flanking Region↗

PubMed1992

Differential trans-activation of muscle-specific regulatory elements including the mysosin light chain box by chicken MyoD, myogenin, and MRF4.

We have isolated cDNAs encoding a chicken homologue of MRF4 (cMRF4) in addition to chicken MyoD (CMD1) and myogenin (c-myogenin) described previously. In an attempt to understand the roles that cMRF4, CMD1, and c-myogenin play in chicken myogenesis, the effects of these factors on muscle-specific cis-elements identified in regulatory regions of myosin alkali light chain (MLC) genes were examined. The promoter analysis of some of MLC genes has revealed two sorts of muscle-specific positive regulatory elements to date, an enhancer located upstream of the adult type LC1 gene and a cis-element, termed an MLC box, conserved among promoters of various MLC genes. The LC1 enhancer was exclusively trans-activated by CMD1. Although c-myogenin also activated transcription driven by the LC1 promoter, it was suggested that c-myogenin requires a cis-element(s) other than the CMD1-responsive enhancer. Chicken MRF4 could not trans-activate any of the constructs containing the LC1 promoter. In contrast, the promoter of the embryonic L23 gene was trans-activated by all of the three factors. From deletion and mutation analysis, the MLC box was shown to be involved in their positive regulation. These results extend previous observations that individual myogenic regulatory factors exhibit different capabilities in transcriptional activation of muscle-specific genes by acting distinctively upon their regulatory elements.

Amino Acid Sequence↗