Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter.

Neuman E; Flemington EK; Sellers WR; Kaelin WG Jr

Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

Mol Cell Biol 14: 6607-15 (1994)

Abstract
The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fused to a luciferase cDNA, gave rise to cell cycle-dependent luciferase activity upon transfection into mammalian cells in a manner which paralleled previously reported changes in E2F-1 mRNA abundance. The E2F-1 promoter contains four potential E2F-binding sites organized as two imperfect palindromes. Gel shift and transactivation studies suggested that these sites can bind to E2F in vitro and in vivo. Mutation of the two E2F palindromes abolished the cell cycle dependence of the E2F-1 promoter. Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter.

Mesh Headings

Animal

Aspergillus Nuclease S1

Base Sequence

Cell Cycle*

Cells, Cultured

Cloning, Molecular

DNA Mutational Analysis

DNA-Binding Proteins

Human

Mice

Molecular Sequence Data

Polymerase Chain Reaction

Promoter Regions (Genetics)*

Protein Binding

Recombinant Fusion Proteins

Sequence Analysis, DNA

Sequence Deletion

Support, Non-U.S. Gov't

Support, U.S. Gov't, P.H.S.

Transcription Factors*

Transcription, Genetic*

Unique Identifier: 95021188

Chemical Identifiers (Names)

EC 3.1.30.1 (Aspergillus Nuclease S1)

(transcription factor E2F)

(DNA-Binding Proteins)

(Recombinant Fusion Proteins)

(Transcription Factors)