Sequences containing the second-intron enhancer are essential for transcription of the human apolipoprotein B gene in the livers of transgenic mice.

Abstract:

:To identify DNA sequence elements from the human apolipoprotein B (apoB) gene required for high-level, correct tissue-specific expression in transgenic mice, we made several constructs that included one or more of the key regulatory elements that were previously characterized with cultured liver-derived and intestine-derived cell lines. Our data show that the apoB promoter alone (-898 to +121) is not sufficient to direct transcription in transgenic mice. An enhancer located in the second intron is absolutely required to specify transcription by the homologous apoB promoter in the livers of transgenic mice; this enhancer does not direct transcription in the small intestines. Thus, the elements controlling transcriptional activation of the apoB gene in the liver and the intestine in vivo are distinct and separable. Analysis of the DNase I hypersensitivity of the integrated human transgenes in various lines of expressing and nonexpressing mice suggests that the formation of DH4, a strong hypersensitive site in intron 2, may be a prerequisite for hepatic expression of the apoB gene. Nuclear matrix association regions (MARs) of the apoB gene may play a role in transgene expression. Constructs including MAR sequences displayed higher levels of expression than those lacking them. However, these MARs did not completely insulate the associated transgenes from position effects.

journal_name

Mol Cell Biol

authors

Brooks AR,Nagy BP,Taylor S,Simonet WS,Taylor JM,Levy-Wilson B

doi

10.1128/mcb.14.4.2243

subject

Has Abstract

pub_date

1994-04-01 00:00:00

pages

2243-56

issue

4

eissn

0270-7306

issn

1098-5549

journal_volume

14

pub_type

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