Abstract
Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment.
Highlights
Transcription factors (TFs) include the most prominent regulatory proteins that bind to the specific region in the DNA and control gene expression by influencing RNA polymerase activity [1, 2]
The study of the transcriptional apparatus and their associated proteins are continually renewing with advanced information available that can be used in various perspectives to target and regulate gene expression
The molecular characterization of the deregulated TF and associated pathogenesis is of great concern and should point to therapeutic approaches
Summary
Transcription factors (TFs) include the most prominent regulatory proteins that bind to the specific region in the DNA and control gene expression by influencing RNA polymerase activity [1, 2]. ER functions as part of a sizeable transcriptional complex involving multiple TFs, including its pioneer factor, FOXA1, GATA binding protein 3 (GATA3), pre-B-cell leukemia transcription factor 1 (PBX1), and transducin-like enhancer protein 1 (TLE1) Many of these modulate the ER pathway activity by directly affecting the binding of ER to chromatin [9]. The activated ERα binds to genomic DNA with numerous other proteins, including pioneer factor facilitating a permissive state of gene expression. Steroid receptors such as ER and androgen receptor (AR) exhibit pioneer properties in a chromatin dependent manner. A recent study encompassing genomic analysis of FOXA1 associated with hormonal cancers showed that FOXA1 binding events are not regulated by hormones [34]
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