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Titolo:
CHARACTERIZATION OF MULTIPLE ENHANCER REGIONS UPSTREAM OF THE APOLIPOPROTEIN(A) GENE
Autore:
WADE DP; PUCKEY LH; KNIGHT BL; ACQUATI F; MIHALICH A; TARAMELLI R;
Indirizzi:
ROYAL POSTGRAD MED SCH,MRC,LIPOPROT TEAM,CTR CLIN SCI,DUCANE RD LONDON W12 0NN ENGLAND HAMMERSMITH HOSP,MRC,LIPOPROT TEAM,CTR CLIN SCI LONDON W12 0NN ENGLAND SAN RAFFAELE SCI INST I-20132 MILAN ITALY UNIV CATANIA,DIPARTIMENTO BIOL ANIM I-95124 CATANIA ITALY
Titolo Testata:
The Journal of biological chemistry
fascicolo: 48, volume: 272, anno: 1997,
pagine: 30387 - 30399
SICI:
0021-9258(1997)272:48<30387:COMERU>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMA LIPOPROTEIN(A) CONCENTRATION; HORMONE RECEPTOR SUPERFAMILY; CORONARY HEART-DISEASE; APO(A) MESSENGER-RNA; TRANS-ACTING FACTOR; TRANSCRIPTION FACTOR; PEROXISOME PROLIFERATORS; HYPERSENSITIVE SITES; TRANSPOSABLE ELEMENT; SIZE HETEROGENEITY;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
80
Recensione:
Indirizzi per estratti:
Citazione:
D.P. Wade et al., "CHARACTERIZATION OF MULTIPLE ENHANCER REGIONS UPSTREAM OF THE APOLIPOPROTEIN(A) GENE", The Journal of biological chemistry, 272(48), 1997, pp. 30387-30399

Abstract

Plasma concentrations of the atherogenic lipoprotein(a) (Lp(a)) are predominantly determined by inherited sequences within or closely linked to the apolipoprotein(a) gene locus, Much of the interindividual variability in Lp(a) levels is likely to originate at the level of apo(a)gene transcription, However, the liver-specific apo(a) basal promoteris extremely weak and does not exhibit common functional variations that affect plasma Lp(a) concentrations, In a search for additional apo(a) gene control elements, we have identified two fragments with enhancer activity within the 40-kilobase pair apo(a)-plasminogen intergenicregion that coincide with DNase I-hypersensitive sites (DHII and DHIII) observed in liver chromatin of mice expressing a human apo(a) transgene. Neither enhancer exhibits tis sue specificity. DHIII activity was mapped to a BOG-base pair fragment containing nine DNase I-protectedelements (footprints) that stimulates luciferase expression from the apo(a) promoter 10-15-fold in HepG2 cells, Binding of the ubiquitous transcription factor Spl plays a major role in the function of this enhancer, but no single site was indispensable for activity, DHIII com prises part of the regulatory region of an inactive long interspersed nucleotide element 1 retrotransposon, raising the possibility that retrotransposon insertion can influence the regulation of adjacent genes. DHII enhancer activity was localized to a 180-base pair fragment that stimulates transcription from the aps(a) promoter 4-8-fold in HepG2 cells. Mutations within an Spl site or either of two elements composed ofdirect repeats of the nuclear hormone receptor half-site AGGTCA in this sequence completely abolished enhancer function. Both nuclear hormone receptor elements were shown to bind peroxisome proliferator-activated receptors and other members of the nuclear receptor family, suggesting that this enhancer may mediate drug and hormone responsiveness.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 11:25:50