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PMID: 2325642 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of positive and negative regulatory elements governing cell-type-specific expression of the neural cell adhesion molecule gene.

Molecular and cellular biology ·Vol. 10 ·No. 5 ·1990-05-00 ·Pages 1959-68

Hirsch MR, Gaugler L, Deagostini-Bazin H, Bally-Cuif L, Goridis C

Abstract

The neural cell adhesion molecule (NCAM) is one of the most prevalent cell adhesion molecules in vertebrates. Its expression is subject to complex cell-type- and developmental-stage-dependent regulation. To study this regulation at the level of transcription, we analyzed the promoter region of the mouse NCAM gene. The NCAM promoter did not contain a typical TATA box. Transcription started at several sites that were used indiscriminately by different cell types, implying that the different NCAM isoforms are expressed from a single promoter. Sequences responsible for both promotion and inhibition of transcription resided within 840 base pairs upstream of the main transcriptional start site. The sequence from positions -645 to -37 relative to the translation initiation site directed high levels of expression in NCAM-expressing N2A cells. The same fragment was six times less active but still significantly active in L cells, but this activity was repressed by inclusion of an additional upstream segment. We mapped eight domains of interactions with nuclear proteins within the 840-base-pair region. The segment with maximum promoter activity contained two adjacent footprints, the occupation of which appeared to be mutually exclusive. One of them corresponded to an Sp1-factor-binding consensus site, the other one bound a factor with nuclear factor I activity. The single protected domain in the fragment harboring a repressor activity consisted of a GGA repeat resembling negative regulatory elements in other promoters. Three adjacent binding sites occupied an A + T-rich segment and contained ATTA motifs also found in the recognition elements of homeodomain proteins. These results show that negative and positive elements interact to regulate the tissue-specific patterns of expression of the NCAM gene and indicate that a factor related to nuclear factor I is involved in its transcriptional control.

MeSH Terms
Animals Base Sequence Cell Adhesion Molecules, Neuronal/genetics Cell Nucleus/physiology Cloning, Molecular Deoxyribonuclease I/pharmacology Gene Expression Regulation In Vitro Techniques Mice Molecular Sequence Data Promoter Regions, Genetic Regulatory Sequences, Nucleic Acid Restriction Mapping Transcription, Genetic
Chemicals
Cell Adhesion Molecules, Neuronal Deoxyribonuclease I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hirsch M R
Centre d'Immunologie Institut National de la Santé, Marseille-Luminy, France.
Gaugler L
Deagostini-Bazin H
Bally-Cuif L
Goridis C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.10.5.1959-1968.1990
Published
1990-05-00
Pages
1959-68
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360542
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.10.5.1959-1968.1990 PMC Full Text View journal details
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