scholarly journals Nutrient and hormonal regulation of pyruvate kinase gene expression

1998 ◽  
Vol 337 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Kazuya YAMADA ◽  
Tamio NOGUCHI
Keyword(s):  
Pyruvate Kinase ◽  
Hormonal Regulation ◽  
Regulatory Elements ◽  
Glycolytic Enzyme ◽  
Hormonal Control ◽  
Nuclear Factor ◽  
Alternative Promoters ◽  
Kinase Gene ◽  
Flanking Region ◽  
Nuclear Factor 1

Mammalian pyruvate kinase (PK), a key glycolytic enzyme, has two genes named PKL and PKM, which produce the L- and R-type isoenzymes by means of alternative promoters, and the M1-and M2-types by mutually exclusive alternative splicing respectively. The expression of these genes is tissue-specific and under developmental, dietary and hormonal control. The L-type isoenzyme (L-PK) gene contains multiple regulatory elements necessary for regulation in the 5´ flanking region, up to position -170. Both L-II and L-III elements are required for stimulation of L-PK gene transcription by carbohydrates such as glucose and fructose, although the L-III element is itself responsive to carbohydrates. The L-II element is also responsible for the gene regulation by polyunsaturated fatty acids. Nuclear factor-1 proteins and hepatocyte nuclear factor 4, which bind to the L-II element, may also be involved in carbohydrate and polyunsaturated fatty acid regulation of the L-PK gene respectively. However, the L-III-element-binding protein that is involved in carbohydrate regulation remains to be clarified, although involvement by an upstream stimulating factor has been proposed. Available evidence suggests that the carbohydrate signalling pathway to the L-PK gene includes a glucose metabolite, possibly glucose 6-phosphate or xylulose 5-phosphate, as well as phosphorylation and dephosphorylation mechanisms. In addition, at least five regulatory elements have been identified in the 5´ flanking region of the PKM gene up to position -279. Sp1-family proteins bind to two proximal elements, but the binding of proteins to other elements have not yet been clarified. Glucose may stimulate the transcription of the PKM gene via hexosamine derivatives. Sp1 may be involved in this regulation via its dephosphorylation, although the carbohydrate response element has not been determined precisely in the PKM gene. Thus glucose stimulates transcription of the PKM gene by the mechanism which is probably different from the L-PK gene.

scholarly journals Nuclear Factor 1 Family Members Interact with Hepatocyte Nuclear Factor 1α to Synergistically Activate L-type Pyruvate Kinase Gene Transcription

2005 ◽  
Vol 280 (48) ◽  
pp. 39827-39834 ◽  
Author(s):  
Shin-ichi Satoh ◽  
Takashi Noaki ◽  
Tatsuya Ishigure ◽  
Shigehiro Osada ◽  
Masayoshi Imagawa ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Gene Transcription ◽  
Family Members ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Kinase Gene ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Nuclear Factor 1

scholarly journals Analysis by cell-free transcription of the liver-specific pyruvate kinase gene promoter.

1989 ◽  
Vol 9 (10) ◽  
pp. 4409-4415 ◽  
Author(s):  
S Vaulont ◽  
N Puzenat ◽  
A Kahn ◽  
M Raymondjean
Keyword(s):  
Binding Site ◽  
Pyruvate Kinase ◽  
Gene Promoter ◽  
Specific Factor ◽  
Nuclear Factor ◽  
Flanking Sequence ◽  
Kinase Gene ◽  
Cell Extracts ◽  
Nuclear Factor 1

A DNA fragment spanning nucleotides -183 to -4 with respect to the cap site of the rat L-type pyruvate kinase (L-PK) gene contains at least four binding sites for putative transcriptional factors: hepatocyte nuclear factor 1 (HNF1), liver factor A1 (LF-A1), nuclear factor 1 (NF1), and major late transcription factor (MLTF). This fragment was used to direct transcription of a reporter sequence (a G-free cassette) in cell extracts. This L-PK promoter was active in liver nuclear extracts, but not in extracts from nonhepatic tissues. A reduction of 50% of the activity was obtained with a deleted L-PK promoter containing only the HNF1-binding site. In contrast, deletion of the HNF1-binding site inactivated the promoter by more than 90%. These results were confirmed by titration experiments with synthetic oligonucleotides. Titration of HNF1 resulted in an 85% decrease of transcriptional activity, while titration of LF-A1 resulted in only a 40% decrease. The influence of NF1 and MLTF seemed to be marginal in this system. The proximal 5'-flanking sequence of the L-PK gene therefore appears to function in vitro as an efficient liver-specific promoter which requires the binding of the liver factor HNF1 and which is also stimulated by the binding of another liver-specific factor, LF-A1.

Analysis by cell-free transcription of the liver-specific pyruvate kinase gene promoter

1989 ◽  
Vol 9 (10) ◽  
pp. 4409-4415
Author(s):  
S Vaulont ◽  
N Puzenat ◽  
A Kahn ◽  
M Raymondjean
Keyword(s):  
Binding Site ◽  
Pyruvate Kinase ◽  
Gene Promoter ◽  
Specific Factor ◽  
Nuclear Factor ◽  
Flanking Sequence ◽  
Kinase Gene ◽  
Cell Extracts ◽  
Nuclear Factor 1

A DNA fragment spanning nucleotides -183 to -4 with respect to the cap site of the rat L-type pyruvate kinase (L-PK) gene contains at least four binding sites for putative transcriptional factors: hepatocyte nuclear factor 1 (HNF1), liver factor A1 (LF-A1), nuclear factor 1 (NF1), and major late transcription factor (MLTF). This fragment was used to direct transcription of a reporter sequence (a G-free cassette) in cell extracts. This L-PK promoter was active in liver nuclear extracts, but not in extracts from nonhepatic tissues. A reduction of 50% of the activity was obtained with a deleted L-PK promoter containing only the HNF1-binding site. In contrast, deletion of the HNF1-binding site inactivated the promoter by more than 90%. These results were confirmed by titration experiments with synthetic oligonucleotides. Titration of HNF1 resulted in an 85% decrease of transcriptional activity, while titration of LF-A1 resulted in only a 40% decrease. The influence of NF1 and MLTF seemed to be marginal in this system. The proximal 5'-flanking sequence of the L-PK gene therefore appears to function in vitro as an efficient liver-specific promoter which requires the binding of the liver factor HNF1 and which is also stimulated by the binding of another liver-specific factor, LF-A1.

Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae

1989 ◽  
Vol 9 (2) ◽  
pp. 442-451
Author(s):  
M Nishizawa ◽  
R Araki ◽  
Y Teranishi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Pyruvate Kinase ◽  
Transcriptional Activation ◽  
Regulatory Elements ◽  
Noncoding Region ◽  
Yeast Cells ◽  
Kinase Gene ◽  
Yeast Saccharomyces Cerevisiae ◽  
Upstream Activating Sequence

To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UASPYK1) located between 634 and 653 nucleotides upstream of the initiating ATG codon. The promoter activity of the PYK 5'-noncoding region was abolished when the sequence containing the UASPYK1 was deleted from the region. Synthetic UASPYK1 (26mer), in either orientation, was able to restore the transcriptional activity of UAS-depleted mutants when placed upstream of the TATA sequence located at -199 (ATG as +1). While the UASPYK1 was required for basal to intermediate levels of transcriptional activation, a sequence between -714 and -811 was found to be necessary for full activation. On the other hand, a sequence between -344 and -468 was found to be responsible for transcriptional repression of the PYK gene when yeast cells were grown on nonfermentable carbon sources. This upstream repressible sequence also repressed transcription, although to a lesser extent, when glucose was present in the medium. The possible mechanism for carbon source-dependent regulation of PYK expression through these cis-acting regulatory elements is discussed.

scholarly journals Hepatic transcription of the acute-phase alpha 1-inhibitor III gene is controlled by a novel combination of cis-acting regulatory elements.

1990 ◽  
Vol 10 (7) ◽  
pp. 3483-3491 ◽  
Author(s):  
L J Abraham ◽  
A D Bradshaw ◽  
B R Shiels ◽  
W Northemann ◽  
G Hudson ◽  
...  
Keyword(s):  
Binding Sites ◽  
Transcriptional Start Site ◽  
Regulatory Elements ◽  
Nuclear Factor ◽  
Base Pairs ◽  
Cis Acting ◽  
Expression Studies ◽  
Positive Regulators ◽  
Flanking Region ◽  
Related Proteins

mRNA coding for the abundant broad-range plasma proteinase inhibitor alpha 1-inhibitor III (alpha 1I3) was detected only in rat liver, while mRNA for the related proteins alpha 1-macroglobulin and alpha 2-macroglobulin was also found in a variety of nonhepatic tissues. cis-Acting control elements necessary for the hepatic transcription of alpha 1I3 were mapped by transfection and expression studies of control-region constructs in cultured hepatic and nonhepatic cells. The promoter-proximal 5'-flanking region contained four control elements, I to IV, located between -109 and -196 base pairs upstream of the transcriptional start site relevant for the hepatic transcription of this gene. Elements II and III were essential, and I and IV exerted strong modulatory effects. Elements I to III acted as positive regulators, and IV acted as a negative element. Element II contained the sequence TGGCA and is probably a binding site for a nuclear factor related to the known transcription factor NF1. The other three elements did not resemble consensus binding sites for known transcription factors that are involved in the hepatocyte-specific transcription of other well-characterized plasma protein genes, such as the prototype factor HNF-1. Thus, the alpha 1I3 gene achieves its highly hepatocyte-specific transcription through a novel combination of cis-acting control elements and trans-acting factors.

scholarly journals The Forkhead Factor FoxE1 Binds to the Thyroperoxidase Promoter during Thyroid Cell Differentiation and Modifies Compacted Chromatin Structure

2007 ◽  
Vol 27 (20) ◽  
pp. 7302-7314 ◽  
Author(s):  
Isabel Cuesta ◽  
Kenneth S. Zaret ◽  
Pilar Santisteban
Keyword(s):  
Chromatin Structure ◽  
Hormonal Regulation ◽  
Specific Factor ◽  
Thyroid Cell ◽  
Nuclear Factor ◽  
Forkhead Box ◽  
Pioneer Factor ◽  
Nuclear Factor 1 ◽  
Hormone Responsiveness

ABSTRACT The Forkhead box (Fox) transcription factors play diverse roles in differentiation, development, hormone responsiveness, and aging. A pioneer activity of the Forkhead factors in developmental processes has been reported, but how this may apply to other contexts of Forkhead factor regulation remains unexplored. In this study, we address the pioneer activity of the thyroid-specific factor FoxE1 during thyroid differentiation. In response to hormone induction, FoxE1 binds to the compacted chromatin of the inactive thyroperoxidase (TPO) promoter, which coincides with the appearance of strong DNase I hypersensitivity at the FoxE1 binding site. In vitro, FoxE1 can bind to its site even when this is protected by a nucleosome, and it creates a local exposed domain specifically on H1-compacted TPO promoter-containing nucleosome arrays. Furthermore, nuclear factor 1 binds to the TPO promoter simultaneously with FoxE1, and this binding has an additive effect on FoxE1-mediated chromatin structure alteration. On the basis of our findings, we propose that FoxE1 is a pioneer factor whose primary mechanistic role in mediating the hormonal regulation of the TPO gene is to enable other regulatory factors to access the chromatin. The presented model extends the reported pioneer activity of the Forkhead factors to processes involved in hormone-induced differentiation.

Nuclear Factor-1 Motif and Redundant Regulatory Elements Comprise Phenobarbital-Responsive Enhancer inCYP2B1/2

1998 ◽  
Vol 17 (5) ◽  
pp. 461-470 ◽  
Author(s):  
SIQING LIU ◽  
YOUNGKYU PARK ◽  
ILIA RIVERA-RIVERA ◽  
HONG LI ◽  
BYRON KEMPER
Keyword(s):  
Regulatory Elements ◽  
Nuclear Factor ◽  
Nuclear Factor 1

Hepatic transcription of the acute-phase alpha 1-inhibitor III gene is controlled by a novel combination of cis-acting regulatory elements

1990 ◽  
Vol 10 (7) ◽  
pp. 3483-3491
Author(s):  
L J Abraham ◽  
A D Bradshaw ◽  
B R Shiels ◽  
W Northemann ◽  
G Hudson ◽  
...  
Keyword(s):  
Binding Sites ◽  
Transcriptional Start Site ◽  
Regulatory Elements ◽  
Nuclear Factor ◽  
Base Pairs ◽  
Cis Acting ◽  
Expression Studies ◽  
Positive Regulators ◽  
Flanking Region ◽  
Related Proteins

mRNA coding for the abundant broad-range plasma proteinase inhibitor alpha 1-inhibitor III (alpha 1I3) was detected only in rat liver, while mRNA for the related proteins alpha 1-macroglobulin and alpha 2-macroglobulin was also found in a variety of nonhepatic tissues. cis-Acting control elements necessary for the hepatic transcription of alpha 1I3 were mapped by transfection and expression studies of control-region constructs in cultured hepatic and nonhepatic cells. The promoter-proximal 5'-flanking region contained four control elements, I to IV, located between -109 and -196 base pairs upstream of the transcriptional start site relevant for the hepatic transcription of this gene. Elements II and III were essential, and I and IV exerted strong modulatory effects. Elements I to III acted as positive regulators, and IV acted as a negative element. Element II contained the sequence TGGCA and is probably a binding site for a nuclear factor related to the known transcription factor NF1. The other three elements did not resemble consensus binding sites for known transcription factors that are involved in the hepatocyte-specific transcription of other well-characterized plasma protein genes, such as the prototype factor HNF-1. Thus, the alpha 1I3 gene achieves its highly hepatocyte-specific transcription through a novel combination of cis-acting control elements and trans-acting factors.

scholarly journals Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae.

1989 ◽  
Vol 9 (2) ◽  
pp. 442-451 ◽  
Author(s):  
M Nishizawa ◽  
R Araki ◽  
Y Teranishi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Pyruvate Kinase ◽  
Transcriptional Activation ◽  
Regulatory Elements ◽  
Noncoding Region ◽  
Yeast Cells ◽  
Kinase Gene ◽  
Yeast Saccharomyces Cerevisiae ◽  
Upstream Activating Sequence

To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UASPYK1) located between 634 and 653 nucleotides upstream of the initiating ATG codon. The promoter activity of the PYK 5'-noncoding region was abolished when the sequence containing the UASPYK1 was deleted from the region. Synthetic UASPYK1 (26mer), in either orientation, was able to restore the transcriptional activity of UAS-depleted mutants when placed upstream of the TATA sequence located at -199 (ATG as +1). While the UASPYK1 was required for basal to intermediate levels of transcriptional activation, a sequence between -714 and -811 was found to be necessary for full activation. On the other hand, a sequence between -344 and -468 was found to be responsible for transcriptional repression of the PYK gene when yeast cells were grown on nonfermentable carbon sources. This upstream repressible sequence also repressed transcription, although to a lesser extent, when glucose was present in the medium. The possible mechanism for carbon source-dependent regulation of PYK expression through these cis-acting regulatory elements is discussed.

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