Promoter and Cofactor Requirements for SERM-ER Activity

Abstract

The mechanism by which Estrogen Receptor regulates transcription is poorly understood. We aimed to identify, in an unbiased manner, DNA elements and proteins that augment or inhibit ER activity in vivo. We used a combination of Chromatin Immunoprecipitation (Chip) with various novel approaches to identify contributing factors. We initially mapped ER binding using Chip in combination with tiling microarrays that cover the entire non-repetitive sequence of chromosomes 21 and 22. This study resulted in several novel conclusions, including the fact that ER rarely binds to promoter regions but uses distal enhancer and that these distal enhancers are defined by the presence of a Forkhead protein, namely FoxA1. We also showed that FoxA1 is essential for ER binding to the chromatin and for subsequent gene transcription. More recently, we have extended on these findings and have mapped all in vivo ER and RNA Polymerase II binding sites in a breast cancer cell line. We are currently mining this large dataset, but have already found a number of novel ER associated proteins that appear to be essential for ER-mediated transcription.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
May 01, 2006
Accession Number
ADA452289

Entities

People

  • Jason S. Carroll

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chromosome Structures
  • Chromosomes
  • Computational Biology
  • Deoxyribonucleic Acids
  • Gene Expression
  • Growth Factors
  • Human Genome
  • Identification
  • Neoplasms
  • Probability
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology
  • Computer science

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and genetic basis of cancer.