scholarly journals Separate Cis-acting DNA Elements Control Cell Type- and Tissue-specific Expression of Collagen Binding Molecular Chaperone HSP47

1999 ◽  
Vol 274 (50) ◽  
pp. 35703-35710 ◽  
Author(s):  
Hiromi Hirata ◽  
Isao Yamamura ◽  
Kunihiko Yasuda ◽  
Akio Kobayashi ◽  
Norihiro Tada ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
Control Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Collagen Binding ◽  
Tissue Specific ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Dna Elements

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice

1991 ◽  
Vol 11 (7) ◽  
pp. 3564-3572 ◽  
Author(s):  
J W Chamberlain ◽  
H A Vasavada ◽  
S Ganguly ◽  
S M Weissman
Keyword(s):  
Major Histocompatibility Complex ◽  
Transgenic Mice ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Histocompatibility Complex

We previously reported that genomic major histocompatibility complex class I human leukocyte antigen (HLA)-B7 gene constructs with as little as 0.66 kb of 5'- and 2.0 kb of 3'-flanking DNA were expressed efficiently and appropriately in transgenic mice. To identify and characterize the relevant cis-acting regulatory elements in more detail, we have generated and analyzed a series of transgenic mice carrying native HLA-B7 genes with further 5' truncations or intronic deletions and hybrid constructs linking the 5'-flanking region of B7 to a reporter gene. We were unable to detect a specific requirement for sequence information within introns 2 to 7 for either appropriate constitutive or inducible class I expression in adult animals. The results revealed the presence of cis-acting regulatory sequences between -0.075 kb and -0.66 kb involved in driving efficient copy number-dependent constitutive and gamma interferon-enhanced tissue-specific expression. The region from -0.11 to -0.66 kb is also sufficient to prevent integration site-specific "position effects," because in its absence HLA-B7 expression is frequently detected at significant levels at inappropriate sites. Conserved sequence elements homologous to the H-2 class I regulatory element, or enhancer A, and the interferon response sequence are located between about -151 and -228 bp of the B7 gene. Our results also indicate the existence of sequences downstream of -0.11 kb which can influence the pattern of tissue-specific expression of the HLA-B7 gene and the ability of this gene to respond to gamma interferon.

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.

scholarly journals Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice.

1990 ◽  
Vol 10 (6) ◽  
pp. 2521-2527 ◽  
Author(s):  
P Greer ◽  
V Maltby ◽  
J Rossant ◽  
A Bernstein ◽  
T Pawson
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Specific Expression ◽  
Tissue Specific ◽  
Protein Tyrosine ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Pair Fragment

The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid lineage. To determine the limits of the c-fps/fes locus and to investigate the cis-acting sequences required to direct appropriate tissue-specific expression, a 13-kilobase-pair fragment of human genomic DNA containing the entire c-fps/fes coding sequence was introduced into the mouse germ line. Transcription of the human c-fps/fes transgene was highest in bone marrow and showed a tissue distribution identical to that of the endogenous mouse gene. Macrophages cultured from transgenic mouse bone marrow contained particularly high levels of human and murine c-fps/fes RNA. Furthermore, expression of human c-fps/fes RNA induced a proportionate increase in the level of the p92c-fes protein-tyrosine kinase in bone marrow, bone marrow-derived macrophages, and spleen. Elevated levels of normal human p92c-fes had no obvious effect on mouse development or hematopoiesis. Remarkably, given the short 5'- and 3'-flanking sequences, expression of the human proto-oncogene in bone marrow was independent of integration site, was proportional to the transgene copy number, and was of comparable efficiency to that of the endogenous mouse c-fps/fes gene. The 13-kilobase-pair fragment therefore defines a genetic locus sufficient for the appropriate tissue-specific expression of the fps/fes protein-tyrosine kinase and includes a dominant cis-acting element that directs integration-independent myeloid expression in transgenic mice.

scholarly journals Cell-type and Tissue-specific Expression of Caveolin-2

1997 ◽  
Vol 272 (46) ◽  
pp. 29337-29346 ◽  
Author(s):  
Philipp E. Scherer ◽  
Renée Y. Lewis ◽  
Daniela Volonté ◽  
Jeffrey A. Engelman ◽  
Ferruccio Galbiati ◽  
...  
Keyword(s):  
Cell Type ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice

1990 ◽  
Vol 10 (6) ◽  
pp. 2521-2527
Author(s):  
P Greer ◽  
V Maltby ◽  
J Rossant ◽  
A Bernstein ◽  
T Pawson
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Specific Expression ◽  
Tissue Specific ◽  
Protein Tyrosine ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Pair Fragment

The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid lineage. To determine the limits of the c-fps/fes locus and to investigate the cis-acting sequences required to direct appropriate tissue-specific expression, a 13-kilobase-pair fragment of human genomic DNA containing the entire c-fps/fes coding sequence was introduced into the mouse germ line. Transcription of the human c-fps/fes transgene was highest in bone marrow and showed a tissue distribution identical to that of the endogenous mouse gene. Macrophages cultured from transgenic mouse bone marrow contained particularly high levels of human and murine c-fps/fes RNA. Furthermore, expression of human c-fps/fes RNA induced a proportionate increase in the level of the p92c-fes protein-tyrosine kinase in bone marrow, bone marrow-derived macrophages, and spleen. Elevated levels of normal human p92c-fes had no obvious effect on mouse development or hematopoiesis. Remarkably, given the short 5'- and 3'-flanking sequences, expression of the human proto-oncogene in bone marrow was independent of integration site, was proportional to the transgene copy number, and was of comparable efficiency to that of the endogenous mouse c-fps/fes gene. The 13-kilobase-pair fragment therefore defines a genetic locus sufficient for the appropriate tissue-specific expression of the fps/fes protein-tyrosine kinase and includes a dominant cis-acting element that directs integration-independent myeloid expression in transgenic mice.

scholarly journals Multiple cis-acting sequences contribute to evolved regulatory variation for Drosophila Adh genes.

Genetics ◽  
1992 ◽  
Vol 131 (2) ◽  
pp. 333-343
Author(s):  
X M Fang ◽  
M D Brennan
Keyword(s):  
Expression Patterns ◽  
Malpighian Tubules ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Chimeric Genes ◽  
Tissue Specific Expression ◽  
Adh Genes ◽  
Fat Bodies ◽  
Rna Levels

Abstract Drosophila affinidisjuncta and Drosophila hawaiiensis are closely related species that display distinct tissue-specific expression patterns for their homologous alcohol dehydrogenase genes (Adh genes). In Drosophila melanogaster transformants, both genes are expressed at high levels in the larval and adult fat bodies, but the D. affinidisjuncta gene is expressed 10-50-fold more strongly in the larval and adult midguts and Malpighian tubules. The present study reports the mapping of cis-acting sequences contributing to the regulatory differences between these two genes in transformants. Chimeric genes were constructed and introduced into the germ line of D. melanogaster. Stage- and tissue-specific expression patterns were determined by measuring steady-state RNA levels in larvae and adults. Three portions of the promoter region make distinct contributions to the tissue-specific regulatory differences between the native genes. Sequences immediately upstream of the distal promoter have a strong effect in the adult Malpighian tubules, while sequences between the two promoters are relatively important in the larval Malpighian tubules. A third gene segment, immediately upstream of the proximal promoter, influences levels of the proximal Adh transcript in all tissues and developmental stages examined, and largely accounts for the regulatory difference in the larval and adult midguts. However, these as well as other sequences make smaller contributions to various aspects of the tissue-specific regulatory differences. In addition, some chimeric genes display aberrant RNA levels for the whole organism, suggesting close physical association between sequences involved in tissue-specific regulatory differences and those important for Adh expression in the larval and adult fat bodies.

Sign in / Sign up

Export Citation Format

Share Document