Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1995-10-12
pubmed:abstractText
Enhancer elements regulating the neuronal gene, tyrosine hydroxylase (TH), were identified in TH-expressing peripheral nervous system PATH and central nervous system CATH cell lines. Mutational analysis in which rat TH 5'-flanking sequences directed chloramphenicol acetyltransferase (CAT) reporter gene expression demonstrated that mutating the cyclic AMP response element (CRE) at -45 base pair reduced expression by 80-90%. A CRE linked to an enhancerless TH promoter fully supported expression. Cotransfection of a dominant-negative CREB protein reduced expression 50-60%, suggesting that the CRE is bound by CREB or a CREB dimerization partner. Although mutating the AP1/dyad (AD) element at -205 base pair only modestly reduced CAT levels, AD minimal enhancer constructs gave 45-80% of wild type expression when positioned at -91 or -95. However, in its native context at -205, the AD could not support expression. In contrast, a CRE, moved from its normal position at -45 to -206, gave full activity. These results indicate that the CRE is critical for TH transcription in central nervous system CATH and peripheral nervous system PATH cells, whereas the AD is less important and its enhancer activity is context-and/or position-dependent. These results represent the first attempts to map regulatory elements directing TH expression in central nervous system cell lines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21579-89
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7665571-Adrenal Gland Neoplasms, pubmed-meshheading:7665571-Animals, pubmed-meshheading:7665571-Base Sequence, pubmed-meshheading:7665571-Brain Neoplasms, pubmed-meshheading:7665571-Brain Stem, pubmed-meshheading:7665571-Cell Line, pubmed-meshheading:7665571-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:7665571-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:7665571-DNA Mutational Analysis, pubmed-meshheading:7665571-Enhancer Elements, Genetic, pubmed-meshheading:7665571-Gene Expression Regulation, Enzymologic, pubmed-meshheading:7665571-Mice, pubmed-meshheading:7665571-Mice, Transgenic, pubmed-meshheading:7665571-Molecular Sequence Data, pubmed-meshheading:7665571-Mutagenesis, pubmed-meshheading:7665571-Peripheral Nerves, pubmed-meshheading:7665571-Promoter Regions, Genetic, pubmed-meshheading:7665571-Rats, pubmed-meshheading:7665571-Recombinant Proteins, pubmed-meshheading:7665571-Restriction Mapping, pubmed-meshheading:7665571-Transcription, Genetic, pubmed-meshheading:7665571-Transfection, pubmed-meshheading:7665571-Tyrosine 3-Monooxygenase
pubmed:year
1995
pubmed:articleTitle
The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice.
pubmed:affiliation
Neuroscience Program, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.