Genomic Pioneer Factor Underlies Breast Cancer Progression

The use of various molecular and immunofluorescent techniques has identified a pioneer factor known as Pre-B-cell leukemia homeobox 1 (PBX1) which can determine the risk of the spread of cancer in patients with estrogen receptor alpha (ERα)-positive breast cancer.

Scientists at the Dartmouth-Hitchcock Norris Cotton Cancer Center (Lebanon, NH, USA) assessed the prognostic value of PBX1 in breast cancer by performing a meta-analysis using breast tumor expression studies. Pioneer factors are an emerging class of chromatin remodelers with the capacity to modulate cellular identity as they set the stage by defining the genomic regions accessible for transcription factors.

The profile of PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells was accomplished through chromatin immunoprecipitation sequencing (ChIP-seq) and formaldehyde-assisted isolation of regulatory elements sequencing (FAIRE-seq). This revealed that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. The results also demonstrated that PBX1 directly modulates chromatin compaction at discrete genomic regions to promote the recruitment of the transcription factor ERα, driving the proliferative response to estrogen in breast cancer cells.

The authors concluded that their results reveal the intricate interplay between distinct pioneer factors required for the implementation of specific transcriptional response to estrogen in breast cancer and distinguishes PBX1 as a prognostic marker. Mathieu Lupien, PhD, the principal investigator said, "This work may rapidly translate to the clinic because PBX1 could likely serve as a prognostic marker for ERα-positive breast cancer progression. It also highlights the potential therapeutic benefit of developing means to antagonize pioneer factors such as PBX1 to prevent breast cancer progression. The study was published in November 2011 in the open access journal Public Library of Science Genetics.

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Dartmouth-Hitchcock Norris Cotton Cancer Center