MLL3 is a de novo cause of endocrine therapy resistance.

ABSTRACT:

Background

Cancer resequencing studies have revealed epigenetic enzymes as common targets for recurrent mutations. The monomethyltransferase MLL3 is among the most recurrently mutated enzymes in ER+ breast cancer. The H3K4me1 marks created by MLL3 can define enhancers. In ER+ breast cancer, ERα genome-binding sites are primarily distal enhancers. Thus, we hypothesize that mutation of MLL3 will alter the genomic binding and transcriptional regulatory activity of ERα.

Methods

We investigated the genomic consequences of knocking down MLL3 in an MLL3/PIK3CA WT ER+ breast cancer cell line.

Results

Loss of MLL3 led to a large loss of H3K4me1 across the genome, and a shift in genomic location of ERα-binding sites, which was accompanied by a re-organization of the breast canc

SUBMITTER: Stauffer KM 

PROVIDER: S-EPMC8559462 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature