Abstract
We isolated a gene from a mouse pituitary cDNA library that encodes a protein highly homologous to nuclear factor CREB, an activator of cAMP-responsive promoter elements (CREs). We demonstrate that while CREB is expressed uniformly in several cell types, this gene, termed CREM, shows cell-specific expression. CREM has a remarkable organization, since down-stream of the stop codon there is a second, out-of-frame DNA-binding domain. Using PCR and RNAase protection analysis, we have identified three mRNA isoforms that appear to be obtained by differential cell-specific splicing. Sequencing of the isoforms demonstrated alternative usage of the two DNA-binding domains. CREM proteins reveal the same efficiency and specificity of binding to CRE sequences as CREB, but in contrast to CREB, CREM acts as a down-regulator of cAMP-induced transcription.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Blotting, Northern
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Blotting, Southern
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Cell Line
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Cyclic AMP / pharmacology*
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Cyclic AMP Response Element Modulator
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Cyclic AMP Response Element-Binding Protein
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DNA / genetics
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DNA / isolation & purification
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DNA-Binding Proteins / genetics*
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Female
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Gene Library
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Humans
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Mice
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Molecular Sequence Data
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Oligonucleotide Probes
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Pituitary Gland / metabolism
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Placenta / metabolism
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Plasmids
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Polymerase Chain Reaction
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Pregnancy
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Protein Biosynthesis
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RNA, Messenger / genetics
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Repressor Proteins*
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Restriction Mapping
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Sequence Homology, Nucleic Acid
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Transcription, Genetic* / drug effects
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Transfection
Substances
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Oligonucleotide Probes
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RNA, Messenger
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Repressor Proteins
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Cyclic AMP Response Element Modulator
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DNA
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Cyclic AMP