Estrogen receptor α K303R mutation reorganizes its binding to forkhead box protein A1 regions and induces chromatin opening.

ABSTRACT:

Background

Estrogen receptor alpha (ERα) is a frequently mutated gene in breast cancer (BC). While many studies have investigated molecular dysregulation by hotspot mutations at Y537 and D538, which exhibit an estrogen-independent constitutively active phenotype, the functional abnormalities of other mutations remain obscure. The K303R mutation in primary invasive BC has been implicated with endocrine resistance, tumor size, and lymph node positivity. However, the impact of the K303R mutation on the cell epigenome is yet unknown.

Methods and results

We introduced the K303R ERα mutant in ERα-negative MDA-MB-453 cells to monitor ERα-dependent transactivation and to perform epigenomic analyses. ATAC-seq and ChIP-Seq analyses indicated that both wild-type (WT) and the K303R muta

SUBMITTER: Nakadai T 

PROVIDER: S-EPMC9889408 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature