scholarly journals The winged-helix/forkhead protein myocyte nuclear factor β (MNF-β) forms a co-repressor complex with mammalian Sin3B

2000 ◽  
Vol 345 (2) ◽  
pp. 335-343 ◽  
Author(s):  
Quan YANG ◽  
Yanfeng KONG ◽  
Beverly ROTHERMEL ◽  
Daniel J. GARRY ◽  
Rhonda BASSEL-DUBY ◽  
...  
Keyword(s):  
Gene Family ◽  
Transcriptional Repression ◽  
Growth Regulation ◽  
Cellular Proliferation ◽  
Precursor Cells ◽  
Nuclear Factor ◽  
Winged Helix ◽  
Repressor Complex ◽  
Myocyte Nuclear Factor ◽  
Myogenic Precursor

Winged-helix/forkhead proteins regulate developmental events in both invertebrate and vertebrate organisms, but biochemical functions that establish a mechanism of action have been defined for only a few members of this extensive gene family. Here we demonstrate that MNF (myocyte nuclear factor)-β, a winged-helix protein expressed selectively and transiently in myogenic precursor cells of the heart and skeletal muscles, collaborates with proteins of the mammalian Sin3 (mSin3) family to repress transcription. Mutated forms of MNF-β that fail to bind mSin3 are defective in transcriptional repression and in negative growth regulation, an overexpression phenotype revealed in oncogenic transformation assays. These data extend the known repertoire of transcription factors with which mSin3 proteins can function as co-repressors to include members of the winged-helix gene family. Transcriptional repression by MNF-β-mSin3 complexes may contribute to the co-ordination of cellular proliferation and terminal differentiation of myogenic precursor cells.

scholarly journals The winged-helix/forkhead protein myocyte nuclear factor β (MNF-β) forms a co-repressor complex with mammalian Sin3B

2000 ◽  
Vol 345 (2) ◽  
pp. 335 ◽  
Author(s):  
Quan YANG ◽  
Yanfeng KONG ◽  
Beverly ROTHERMEL ◽  
Daniel J. GARRY ◽  
Rhonda BASSEL-DUBY ◽  
...  
Keyword(s):  
Nuclear Factor ◽  
Winged Helix ◽  
Repressor Complex ◽  
Myocyte Nuclear Factor

Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes

1994 ◽  
Vol 14 (7) ◽  
pp. 4596-4605
Author(s):  
R Bassel-Duby ◽  
M D Hernandez ◽  
Q Yang ◽  
J M Rochelle ◽  
M F Seldin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Myogenic Differentiation ◽  
Specific Binding ◽  
Motor Nerve ◽  
Sequence Motif ◽  
Nuclear Factor ◽  
Winged Helix ◽  
Amino Terminal ◽  
Myocyte Nuclear Factor

A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged-helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identity to the winged-helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli.

scholarly journals Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes.

1994 ◽  
Vol 14 (7) ◽  
pp. 4596-4605 ◽  
Author(s):  
R Bassel-Duby ◽  
M D Hernandez ◽  
Q Yang ◽  
J M Rochelle ◽  
M F Seldin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Myogenic Differentiation ◽  
Specific Binding ◽  
Motor Nerve ◽  
Sequence Motif ◽  
Nuclear Factor ◽  
Winged Helix ◽  
Amino Terminal ◽  
Myocyte Nuclear Factor

A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged-helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identity to the winged-helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli.

scholarly journals Mad4 is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc

2003 ◽  
Vol 370 (1) ◽  
pp. 291-298 ◽  
Author(s):  
Louise KIME ◽  
Stephanie C. WRIGHT
Keyword(s):  
Transcriptional Repression ◽  
Cellular Proliferation ◽  
Core Promoter ◽  
Core Promoter Region ◽  
Differentiated Cells ◽  
Chemically Induced ◽  
Proliferation And Differentiation ◽  
Repressor Complex ◽  
Undifferentiated Cells ◽  
Novel Target

Myc and Mad family proteins are central regulators of cellular proliferation and differentiation. We show that various Mad family genes have distinct patterns of expression during the chemically induced differentiation of mouse erythroleukaemia (MEL) cells, suggesting that they each serve a different function. Mad4 RNA is highly induced and persists in terminally differentiated cells, in agreement with observations in other systems. Using reporter gene assays in stably transfected MEL cells, we show that induction of Mad4 is mediated by a 49nt core promoter region. We demonstrate that the initiator element is required for Mad4 activation, and show that induction is associated with the loss from the initiator of a complex that contains Miz-1 and c-Myc. Miz-1 activates the Mad4 promoter in transient transfection assays, and this effect is antagonized by c-Myc. We therefore identify Mad4 as a novel target of transcriptional repression by c-Myc. These data suggest that the expression of Mad4 in proliferating undifferentiated cells is suppressed by the binding of a c-Myc—Miz-1 repressor complex at the initiator, and that the activation of Mad4 during differentiation results, at least in part, from a decrease in c-Myc-mediated repression.

scholarly journals Identification, Expression, and Functions of the Somatostatin Gene Family in Spotted Scat (Scatophagus argus)

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 194
Author(s):  
Peizhe Feng ◽  
Changxu Tian ◽  
Xinghua Lin ◽  
Dongneng Jiang ◽  
Hongjuan Shi ◽  
...  
Keyword(s):  
Gene Family ◽  
Growth Regulation ◽  
Expression Patterns ◽  
Open Reading Frames ◽  
Pcr Analysis ◽  
Sequence Alignments ◽  
Scatophagus Argus ◽  
Gene Structure And Expression ◽  
Liver Fragments

Somatostatins (SSTs) are a family of proteins consisting of structurally diverse polypeptides that play important roles in the growth regulation in vertebrates. In the present study, four somatostatin genes (SST1, SST3, SST5, and SST6) were identified and characterized in the spotted scat (Scatophagus argus). The open reading frames (ORFs) of SST1, SST3, SST5, and SST6 cDNA consist of 372, 384, 321, and 333 bp, respectively, and encode proteins of 123, 127, 106, and 110 amino acids, respectively. Amino acid sequence alignments indicated that all SST genes contained conserved somatostatin signature motifs. Real-time PCR analysis showed that the SST genes were expressed in a tissue specific manner. When liver fragments were cultured in vitro with synthetic peptides (SST1, SST2, or SST6 at 1 μM or 10 μM) for 3 h or 6 h, the expression of insulin-like growth factor 1 and 2 (Igf-1 and Igf-2) in the liver decreased significantly. Treatment with SST5 had no significant effect on Igf-1 and Igf-2 gene expression. This study provides an enhanced understanding of the gene structure and expression patterns of the SST gene family in S. argus. Furthermore, this study provides a foundation for future exploration into the role of SST genes in growth and development.

scholarly journals BRG1 Controls the Activity of the Retinoblastoma Protein via Regulation of p21CIP1/WAF1/SDI

2004 ◽  
Vol 24 (3) ◽  
pp. 1188-1199 ◽  
Author(s):  
Hyeog Kang ◽  
Kairong Cui ◽  
Keji Zhao
Keyword(s):  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Growth Arrest ◽  
Retinoblastoma Protein ◽  
Direct Interaction ◽  
Physical Interaction ◽  
Cdk Inhibitor ◽  
Regulation Of Cell Cycle

ABSTRACT The ubiquitous mammalian chromatin-remodeling SWI/SNF-like BAF complexes play critical roles in tumorigenesis. It was suggested that the direct interaction of BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle progression by pRB. We present evidence that the BRG1-containing complexes regulate the expression of the cdk inhibitor p21CIP1/WAF1/SDI. Furthermore, we show that the physical interaction between BRG1 and pRB is not required for induction of cell growth arrest and transcriptional repression of E2F target genes by pRB. Instead, BRG1 activates pRB by inducing its hypophosphorylation through up-regulation of the cdk inhibitor p21. The hypophosphorylation of pRB is reinforced by down-regulation of critical components, including cdk2, cyclin E, and cyclin D, in the pRB regulatory network. We demonstrate that up-regulation of p21 by BRG1 is necessary to induce formation of flat cells, growth arrest, and finally, cell senescence. Our results suggest that the BRG1-containing complexes control cellular proliferation and senescence by modulating the pRB pathway via multiple mechanisms.

scholarly journals A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter.

1993 ◽  
Vol 13 (3) ◽  
pp. 1610-1618 ◽  
Author(s):  
J E Slansky ◽  
Y Li ◽  
W G Kaelin ◽  
P J Farnham
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Phase Boundary ◽  
Dihydrofolate Reductase ◽  
Transcription Initiation ◽  
Growth Regulation ◽  
Cellular Proliferation ◽  
Protein S ◽  
S Phase ◽  
Dependent Manner

Enhanced expression of genes involved in nucleotide biosynthesis, such as dihydrofolate reductase (DHFR), is a hallmark of entrance into the DNA synthesis (S) phase of the mammalian cell cycle. To investigate the regulated expression of the DHFR gene, we stimulated serum-starved NIH 3T3 cells to synchronously reenter the cell cycle. Our previous results show that a cis-acting element at the site of DHFR transcription initiation is necessary for serum regulation. Recently, this element has been demonstrated to bind the cloned transcription factor E2F. In this study, we focused on the role of E2F in the growth regulation of DHFR. We demonstrated that a single E2F site, in the absence or presence of other promoter elements, was sufficient for growth-regulated promoter activity. Next, we showed that the increase in DHFR mRNA at the G1/S-phase boundary required protein synthesis, raising the possibility that a protein(s) lacking in serum-starved cells is required for DHFR transcription. We found that, similar to DHFR mRNA expression, levels of murine E2F1 mRNA were low in serum-starved cells and increased at the G1/S-phase boundary in a protein synthesis-dependent manner. Furthermore, in a cotransfection experiment, expression of human E2F1 stimulated the DHFR promoter 22-fold in serum-starved cells. We suggest that E2F1 may be the key protein required for DHFR transcription that is absent in serum-starved cells. Expression of E2F also abolished the serum-stimulated regulation of the DHFR promoter and resulted in transcription patterns similar to those seen with expression of the adenoviral oncoprotein E1A. In summary, we provide evidence for the importance of E2F in the growth regulation of DHFR and suggest that alterations in the levels of E2F may have severe consequences in the control of cellular proliferation.

MyoD and Myf-5 define the specification of musculature of distinct embryonic origin

1998 ◽  
Vol 76 (6) ◽  
pp. 1079-1091 ◽  
Author(s):  
Boris Kablar ◽  
Atsushi Asakura ◽  
Kirsten Krastel ◽  
Chuyan Ying ◽  
Linda L May ◽  
...  
Keyword(s):  
Abdominal Wall ◽  
Expression Pattern ◽  
Branchial Arch ◽  
Precursor Cells ◽  
Mouse Development ◽  
Unique Role ◽  
Branchial Arches ◽  
Embryonic Origin ◽  
Body Wall Muscles ◽  
Myogenic Precursor

Mounting evidence supports the notion that Myf-5 and MyoD play unique roles in the development of epaxial (originating in the dorso-medial half of the somite, e.g. back muscles) and hypaxial (originating in the ventro-lateral half of the somite, e.g. limb and body wall muscles) musculature. To further understand how Myf-5 and MyoD genes co-operate during skeletal muscle specification, we examined and compared the expression pattern of MyoD-lacZ (258/-2.5lacZ and MD6.0-lacZ) transgenes in wild-type, Myf-5, and MyoD mutant embryos. We found that the delayed onset of muscle differentiation in the branchial arches, tongue, limbs, and diaphragm of MyoD-/- embryos was a consequence of a reduced ability of myogenic precursor cells to progress through their normal developmental program and not because of a defect in migration of muscle progenitor cells into these regions. We also found that myogenic precursor cells for back, intercostal, and abdominal wall musculature in Myf-5-/-embryos failed to undergo normal translocation or differentiation. By contrast, the myogenic precursors of intercostal and abdominal wall musculature in MyoD-/- embryos underwent normal translocation but failed to undergo timely differentiation. In conclusion, these observations strongly support the hypothesis that Myf-5 plays a unique role in the development of muscles arising after translocation of epithelial dermamyotome cells along the medial edge of the somite to the subjacent myotome (e.g., back or epaxial muscle) and that MyoD plays a unique role in the development of muscles arising from migratory precursor cells (e.g., limb and branchial arch muscles, tongue, and diaphragm). In addition, the expression pattern of MyoD-lacZ transgenes in the intercostal and abdominal wall muscles of Myf-5-/- and MyoD-/- embryos suggests that appropriate development of these muscles is dependent on both genes and, therefore, these muscles have a dual embryonic origin (epaxial and hypaxial).Key words: epaxial and hypaxial muscle, Myf-5, MyoD, mouse development, somite.

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