Natural and synthetic DNA elements with the CArG motif differ in expression and protein-binding properties

1991 ◽  
Vol 11 (12) ◽  
pp. 6296-6305
Author(s):  
I M Santoro ◽  
K Walsh
Keyword(s):  
Constitutive Expression ◽  
Regulatory Elements ◽  
Binding Properties ◽  
Specific Expression ◽  
Tissue Specific ◽  
Left Half ◽  
Tissue Specific Expression ◽  
Dna Elements ◽  
The Right ◽  
Natural And Synthetic

DNA elements with the CC(A/T)6GG, or CArG, motif occur in promoters that are under different regulatory controls. CArG elements from the skeletal actin, c-fos, and myogenin genes were tested for their abilities to confer tissue-specific expression on reporter genes when the individual elements were situated immediately upstream from a TATA element. The c-fos CArG element, also referred to as the serum response element (SRE), conferred basal, constitutive expression on the test promoter. The CArG motif from the myogenin gene was inactive. The skeletal actin CArG motif functioned as a muscle regulatory element (MRE) in that basal expression was detected only in muscle cultures. Muscle-specific expression from the 28-bp MRE and the 2.3-kb skeletal actin promoter was trans repressed by the Fos and Jun proteins. The expression and factor-binding properties of a series of synthetic CArG elements were analyzed. Muscle-specific expression was conferred by perfect 28-bp palindromes on the left and right halves of the skeletal actin MRE. Chimeric elements of the skeletal actin MRE and the c-fos SRE differed in their expression properties. Muscle-specific expression was observed when the left half of the MRE was fused to the right half of the SRE. Constitutive expression was conferred by a chimera with the right half of the MRE fused to the left half of the SRE and by chimeras which exchanged the central CC(A/T)6GG sequences. At least three distinct proteins specifically bound to these CArG elements. The natural and synthetic CArG elements differed in their affinities for these proteins; however, muscle-specific expression could not be attributed to differences in the binding of a single protein. Furthermore, the MRE did not bind MyoD or the myogenin-E12 heterodimer, indicating that muscle-specific expression from this element does not involve a direct interaction with these helix-loop-helix proteins. These data demonstrate that the conserved CArG motifs form the core of a family of functionally different DNA regulatory elements that may contribute to the tissue-specific expression properties of their cognate promoters.

scholarly journals Natural and synthetic DNA elements with the CArG motif differ in expression and protein-binding properties.

1991 ◽  
Vol 11 (12) ◽  
pp. 6296-6305 ◽  
Author(s):  
I M Santoro ◽  
K Walsh
Keyword(s):  
Constitutive Expression ◽  
Regulatory Elements ◽  
Binding Properties ◽  
Specific Expression ◽  
Tissue Specific ◽  
Left Half ◽  
Tissue Specific Expression ◽  
Dna Elements ◽  
The Right ◽  
Natural And Synthetic

DNA elements with the CC(A/T)6GG, or CArG, motif occur in promoters that are under different regulatory controls. CArG elements from the skeletal actin, c-fos, and myogenin genes were tested for their abilities to confer tissue-specific expression on reporter genes when the individual elements were situated immediately upstream from a TATA element. The c-fos CArG element, also referred to as the serum response element (SRE), conferred basal, constitutive expression on the test promoter. The CArG motif from the myogenin gene was inactive. The skeletal actin CArG motif functioned as a muscle regulatory element (MRE) in that basal expression was detected only in muscle cultures. Muscle-specific expression from the 28-bp MRE and the 2.3-kb skeletal actin promoter was trans repressed by the Fos and Jun proteins. The expression and factor-binding properties of a series of synthetic CArG elements were analyzed. Muscle-specific expression was conferred by perfect 28-bp palindromes on the left and right halves of the skeletal actin MRE. Chimeric elements of the skeletal actin MRE and the c-fos SRE differed in their expression properties. Muscle-specific expression was observed when the left half of the MRE was fused to the right half of the SRE. Constitutive expression was conferred by a chimera with the right half of the MRE fused to the left half of the SRE and by chimeras which exchanged the central CC(A/T)6GG sequences. At least three distinct proteins specifically bound to these CArG elements. The natural and synthetic CArG elements differed in their affinities for these proteins; however, muscle-specific expression could not be attributed to differences in the binding of a single protein. Furthermore, the MRE did not bind MyoD or the myogenin-E12 heterodimer, indicating that muscle-specific expression from this element does not involve a direct interaction with these helix-loop-helix proteins. These data demonstrate that the conserved CArG motifs form the core of a family of functionally different DNA regulatory elements that may contribute to the tissue-specific expression properties of their cognate promoters.

The c-fos cyclic AMP-responsive element conveys constitutive expression to a tissue-specific promoter

1990 ◽  
Vol 10 (5) ◽  
pp. 2402-2406
Author(s):  
K A Webster ◽  
L Kedes
Keyword(s):  
Cyclic Amp ◽  
Alternative Pathway ◽  
Constitutive Expression ◽  
Regulatory Elements ◽  
Transcriptional Responses ◽  
Specific Expression ◽  
Tissue Specific ◽  
Actin Promoter ◽  
The Individual ◽  
Alpha Actin

The c-fos and cardiac alpha-actin promoters share homologous 5' protein binding elements that are essential for serum-inducible and tissue-specific expression, respectively. Additional elements, auxiliary proteins or factor modifications, must distinguish the individual transcriptional responses of these two promoters. An element in the c-fos basal promoter that is normally responsible for transient stimulation of the fos gene in response to Ca2+ or cyclic AMP (CRE) may be able to modulate the expression of the upstream elements. We report here that this element, when inserted into the cardiac alpha-actin promoter, conveys constitutive expression to this otherwise highly restricted promoter. Additional data support the proposal that the CRE binding protein creates an alternative pathway whereby upstream regulatory elements in the cardiac alpha-actin promoter can activate transcription in a manner which circumvents the requirement for a tissue-specific environment.

scholarly journals Hypermethylation of human DNA: Fine-tuning transcription associated with development

2017 ◽  
Author(s):  
Carl Baribault ◽  
Kenneth C. Ehrlich ◽  
V. K. Chaithanya Ponnaluri ◽  
Sriharsa Pradhan ◽  
Michelle Lacey ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regulatory Elements ◽  
Fine Tuning ◽  
Ctcf Binding ◽  
Specific Gene ◽  
Dna Hypermethylation ◽  
Specific Expression ◽  
Lncrna Gene ◽  
Tissue Specific ◽  
Tissue Specific Expression

AbstractTissue-specific gene transcription can be affected by DNA methylation in ways that are difficult to discern from studies focused on genome-wide analyses of differentially methylated regions (DMRs). We studied 95 genes in detail using available epigenetic and transcription databases to detect and elucidate less obvious associations between development-linked hypermethylated DMRs in myoblasts (Mb) and cell-and tissue-specific expression. Many of these genes encode developmental transcription factors and display DNA hypermethylation also in skeletal muscle (SkM) and a few heterologous samples (e.g., aorta, mammary epithelial cells, or brain) among the 38 types of human cell cultures or tissues examined. Most of the DMRs overlapped transcription regulatory elements, including canonical, alternative, or cryptic promoters; enhancers; CTCF binding sites; and long-noncoding RNA (lncRNA) gene regions. Among the prominent relationships between DMRs and expression was promoter-region hypermethylation accompanying repression in Mb but not in many other repressed samples (26 genes). Another surprising relationship was down-modulated (but not silenced) expression in Mb associated with DNA hypermethylation at cryptic enhancers in Mb although such methylation was absent in both non-expressing samples and highly expressing samples (24 genes). The tissue-specificity of DNA hypermethylation can be explained for many of the genes by their roles in prenatal development or by the tissue-specific expression of neighboring genes. Besides elucidating developmental epigenetics, our study provides insights into the roles of abnormal DNA methylation in disease, e.g., cancer, Duchenne muscular dystrophy, and congenital heart malformations.

Tissue-specific expression and α-actinin binding properties of the Z-disc titin: implications for the nature of vertebrate Z-discs

1997 ◽  
Vol 270 (5) ◽  
pp. 688-695 ◽  
Author(s):  
H Sorimachi ◽  
A Freiburg ◽  
B Kolmerer ◽  
S Ishiura ◽  
G Stier ◽  
...  
Keyword(s):  
Binding Properties ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

scholarly journals Regulatory elements controlling Ci-msxb tissue-specific expression during Ciona intestinalis embryonic development

2004 ◽  
Vol 267 (2) ◽  
pp. 517-528 ◽  
Author(s):  
Monia Teresa Russo ◽  
Aldo Donizetti ◽  
Annamaria Locascio ◽  
Salvatore D'Aniello ◽  
Alessandro Amoroso ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Ciona Intestinalis ◽  
Regulatory Elements ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression
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