FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4939-4947 ◽  
Author(s):  
L. Liang ◽  
S.M. Soyal ◽  
J. Dean
Keyword(s):  
Transcription Factor ◽  
Zona Pellucida ◽  
Reporter Genes ◽  
Single Copy ◽  
Luciferase Reporter ◽  
Embryonic Fibroblasts ◽  
Transcription Start Sites ◽  
Helix Loop Helix ◽  
E Box ◽  
Dna Complex

The mouse zona pellucida is composed of three glycoproteins, ZP1, ZP2 and ZP3, encoded by single-copy genes whose expression is temporally and spatially restricted to oocytes. All three proteins are required for the formation of the extracellular zona matrix and female mice with a single disrupted zona gene lack a zona and are infertile. An E-box (CANNTG), located approximately 200 bp upstream of the transcription start sites of Zp1, Zp2 and Zp3, forms a protein-DNA complex present in oocytes and, to a much lesser extent, in testes. It has been previously shown that the integrity of this E-box in Zp2 and Zp3 promoters is required for expression of luciferase reporter genes microinjected into growing oocytes. The presence of the ubiquitous transcription factor E12 in the complex was used to identify a novel basic helix-loop-helix protein, FIGalpha (Factor In the Germline alpha) whose expression was limited to oocytes within the ovary. The ability of FIGalpha to transactivate reporter genes coupled to each of the three mouse zona promoters in heterologous 10T(1/2) embryonic fibroblasts suggests a role in coordinating the expression of the three zona pellucida genes during oogenesis.

NeuroM, a neural helix-loop-helix transcription factor, defines a new transition stage in neurogenesis

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3263-3272 ◽  
Author(s):  
T. Roztocil ◽  
L. Matter-Sadzinski ◽  
C. Alliod ◽  
M. Ballivet ◽  
J.M. Matter
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Mitotic Cycle ◽  
Ventricular Zone ◽  
Helix Loop Helix ◽  
E Box ◽  
Genes Encoding ◽  
Developing Nervous System

Genes encoding transcription factors of the helix-loop-helix family are essential for the development of the nervous system in Drosophila and vertebrates. Screens of an embryonic chick neural cDNA library have yielded NeuroM, a novel neural-specific helix-loop-helix transcription factor related to the Drosophila proneural gene atonal. The NeuroM protein most closely resembles the vertebrate NeuroD and Nex1/MATH2 factors, and is capable of transactivating an E-box promoter in vivo. In situ hybridization studies have been conducted, in conjunction with pulse-labeling of S-phase nuclei, to compare NeuroM to NeuroD expression in the developing nervous system. In spinal cord and optic tectum, NeuroM expression precedes that of NeuroD. It is transient and restricted to cells lining the ventricular zone that have ceased proliferating but have not yet begun to migrate into the outer layers. In retina, NeuroM is also transiently expressed in cells as they withdraw from the mitotic cycle, but persists in horizontal and bipolar neurons until full differentiation, assuming an expression pattern exactly complementary to NeuroD. In the peripheral nervous system, NeuroM expression closely follows cell proliferation, suggesting that it intervenes at a similar developmental juncture in all parts of the nervous system. We propose that availability of the NeuroM helix-loop-helix factor defines a new stage in neurogenesis, at the transition between undifferentiated, premigratory and differentiating, migratory neural precursors.

Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factor

1996 ◽  
Vol 151 (3) ◽  
pp. 491-499 ◽  
Author(s):  
Y Liu ◽  
P Cserjesi ◽  
A Nifuji ◽  
E N Olson ◽  
M Noda
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Transcriptional Activity ◽  
Transforming Growth Factor ◽  
Binding Activity ◽  
The Novel ◽  
Helix Loop Helix ◽  
Nuclear Extracts ◽  
E Box ◽  
First Time

Abstract Scleraxis is a recently identified transcription factor with a basic helix-loop-helix motif, which is expressed in sclerotome during embryonic development. We have examined the expression of scleraxis mRNA in rat osteoblastic cells and found that the scleraxis gene was expressed as a 1·2 kb mRNA species in osteoblastic osteosarcoma ROS 17/2·8 cells. The scleraxis mRNA expression was enhanced by type-β transforming growth factor (TGFβ) treatment. The TGFβ effect was observed in a dosedependent manner starting at 0·2 ng/ml and saturating at 2 ng/ml. The effect was time-dependent and was first observed within 12 h and peaked at 24 h. The TGFβ effect was blocked by cycloheximide, while no effect on scleraxis mRNA stability was observed. TGFβ treatment enhanced scleraxis-E box (Scx-E) binding activity in the nuclear extracts of ROS17/2·8 cells. Furthermore, TGFβ enhanced transcriptional activity of the CAT constructs which contain the Scx-E box sequence. TGFβ treatment also enhanced scleraxis gene expression in osteoblastenriched cells derived from primary rat calvaria. These findings indicated for the first time that the novel helixloop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its expression is regulated by TGFβ. Journal of Endocrinology (1996) 151, 491–499

scholarly journals A helix-loop-helix protein related to the immunoglobulin E box-binding proteins.

1990 ◽  
Vol 10 (8) ◽  
pp. 4384-4388 ◽  
Author(s):  
C S Carr ◽  
P A Sharp
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Heavy Chain ◽  
Binding Proteins ◽  
Immunoglobulin E ◽  
Expression Library ◽  
Helix Loop Helix ◽  
E Box ◽  
Late Transcription ◽  
Novel Protein

A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.

A helix-loop-helix protein related to the immunoglobulin E box-binding proteins

1990 ◽  
Vol 10 (8) ◽  
pp. 4384-4388
Author(s):  
C S Carr ◽  
P A Sharp
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Heavy Chain ◽  
Binding Proteins ◽  
Immunoglobulin E ◽  
Expression Library ◽  
Helix Loop Helix ◽  
E Box ◽  
Late Transcription ◽  
Novel Protein

A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.

Murine helix-loop-helix transcriptional activator proteins binding to the E-box motif of the Akv murine leukemia virus enhancer identified by cDNA cloning

1992 ◽  
Vol 12 (8) ◽  
pp. 3449-3459
Author(s):  
A L Nielsen ◽  
N Pallisgaard ◽  
F S Pedersen ◽  
P Jørgensen
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Transcriptional Activator ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box ◽  
Nih 3T3 ◽  
Murine Leukemia

The enhancer region of Akv murine leukemia virus contains the sequence motif ACAGATGG. This sequence is homologous to the E-box motif originally defined as a regulatory element in the enhancers of immunoglobulin mu and kappa genes. We have used double-stranded oligonucleotide probes, corresponding to the E box of the murine leukemia virus Akv, to screen a randomly primed lambda gt11 cDNA expression library made from mouse NIH 3T3 fibroblast RNA. We have identified seven lambda clones expressing DNA-binding proteins representing two different genes termed ALF1 and ALF2. The results of sequencing ALF2 cDNA suggests that we have recovered the gene for the basic-helix-loop-helix transcription factor A1, the murine analog of the human transcription factor E47. The cDNA sequence of ALF1 codes for a new member of the basic-helix-loop-helix protein family. Two splice variants of ALF1 cDNA have been found, differing by a 72-bp insertion, coding for putative proteins of 682 and 706 amino acids. The two ALF1 mRNAs are expressed at various levels in mouse tissues. In vitro DNA binding assays, using prokaryotically expressed ALF1 proteins, demonstrated specific binding of the ALF1 proteins to the Akv murine leukemia virus E-box motif ACAGATGG. Expression in NIH 3T3 fibroblasts of GAL4-ALF1 chimeric protein stimulated expression from a minimal promoter linked to a GAL4 binding site, indicating the existence of a transcriptional activator domain in ALF1.

scholarly journals Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene.

1994 ◽  
Vol 14 (12) ◽  
pp. 8058-8070 ◽  
Author(s):  
K Yasumoto ◽  
K Yokoyama ◽  
K Shibata ◽  
Y Tomita ◽  
S Shibahara
Keyword(s):  
Transcription Factor ◽  
Hela Cells ◽  
Pigment Cell ◽  
Luciferase Reporter ◽  
Enhancer Element ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Tyrosinase Gene ◽  
Helix Structure ◽  
Human Tyrosinase

Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and is specifically expressed in differentiated melanocytes. We have identified the enhancer element in the 5'-flanking region of the human tyrosinase gene that is responsible for its pigment cell-specific transcription and have termed it tyrosinase distal element (TDE) (positions -1861 to -1842). Transient expression assays showed that TDE confers efficient expression of a firefly luciferase reporter gene linked to the tyrosinase gene promoter in MeWo pigmented melanoma cells but not in HeLa cells, which do not express tyrosinase. TDE was specifically bound by nuclear proteins of MeWo and HeLa cells, the binding properties of which were indistinguishable in gel mobility shift assays. TDE contains the CATGTG motif in its center, and mutation analysis indicates that the CA dinucleotides of this motif are crucial for protein binding and pigment cell-specific enhancer function. The CATGTG motif is consistent with the consensus sequence recognized by a large family of transcription factors with a basic helix-loop-helix structure, which prompted us to examine the possible involvement of a ubiquitous transcription factor, USF, and a novel factor, microphthalmia-associated transcription factor (MITF), recently cloned as the human homolog of the mouse microphthalmia (mi) gene product. The mi phenotype is associated with a mutant mi locus and characterized by small eyes and loss of melanin pigments. Both USF and MITF are predicted to contain a basic helix-loop-helix structure and a leucine zipper structure. We provide evidence that USF binds to TDE, whereas we were unable to detect the DNA-binding activity of MITF. Transient coexpression assays showed that MITF specifically transactivates the promoter activity of the tyrosinase gene through the CATGTG motif of TDE but not the promoter of the ubiquitously expressed heme oxygenase gene, while USF is able to activate both promoters. These results indicate that MITF is a cell-type-specific factor that is capable of activating transcription of the tyrosinase gene.

scholarly journals v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

1994 ◽  
Vol 14 (10) ◽  
pp. 6531-6539 ◽  
Author(s):  
W Xie ◽  
B S Fletcher ◽  
R D Andersen ◽  
H R Herschman
Keyword(s):  
Transcription Factor ◽  
Mutational Analysis ◽  
Dominant Negative ◽  
Luciferase Reporter ◽  
Temperature Sensitive ◽  
3T3 Cells ◽  
Ras Gene ◽  
Prostaglandin Synthase ◽  
E Box ◽  
Src Activation

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

scholarly journals Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer.

1994 ◽  
Vol 8 (8) ◽  
pp. 970-980 ◽  
Author(s):  
T Ellenberger ◽  
D Fass ◽  
M Arnaud ◽  
S C Harrison
Keyword(s):  
Crystal Structure ◽  
Transcription Factor ◽  
Helix Loop Helix ◽  
E Box ◽  
Basic Region

scholarly journals The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells

2020 ◽  
Vol 295 (7) ◽  
pp. 2001-2017 ◽  
Author(s):  
M. Carmen Lafita-Navarro ◽  
Judit Liaño-Pons ◽  
Andrea Quintanilla ◽  
Ignacio Varela ◽  
Rosa Blanco ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Transcriptional Regulator ◽  
Bhlh Transcription Factor ◽  
Factor X ◽  
Associated Factor ◽  
Helix Loop Helix ◽  
E Box ◽  
E Boxes ◽  
Cycle Regulation

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC–MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT–MLX and MNT–MAX dimers co-exist. However, all MNT functions have been attributed to MNT–MAX dimers, and no functions of the MNT–MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT–MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT–MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.

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