Pioneer factors in hormone-dependent cancers

Jozwik, Kamila M.; Carroll, Jason S.

doi:10.1038/nrc3263

Cited by 237 publications

(209 citation statements)

References 45 publications

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“…6d). FOXA1, a central transcription factor of prostate cancer biology, coordinates AR binding and promotes tumour progression 31,32 . We observed a significant overlap of the 5-hmC regions with FOXA1-binding regions and K4me1-modified regions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression

et al. 2015

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Modulation of epigenetic patterns has promising efficacy for treating cancer. 5-Hydroxymethylated cytosine (5-hmC) is an epigenetic mark potentially important in cancer. Here we report that 5-hmC is an epigenetic hallmark of prostate cancer (PCa) progression. A member of the ten-eleven translocation (TET) proteins, which catalyse the oxidation of methylated cytosine (5-mC) to 5-hmC, TET2, is repressed by androgens in PCa. Androgen receptor (AR)-mediated induction of the miR-29 family, which targets TET2, are markedly enhanced in hormone refractory PCa (HRPC) and its high expression predicts poor outcome of PCa patients. Furthermore, decreased expression of miR-29b results in reduced tumour growth and increased TET2 expression in an animal model of HRPC. Interestingly, global 5-hmC modification regulated by miR-29b represses FOXA1 activity. A reduction in 5-hmC activates PCa-related key pathways such as mTOR and AR. Thus, DNA modification directly links the TET2-dependent epigenetic pathway regulated by AR to 5-hmC-mediated tumour progression.

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Section: Resultsmentioning

confidence: 99%

TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression

et al. 2015

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“…Thus, ectopic Sox2 expression or a higher level of its expression could activate previously silent programs to establish competence for tumorigenesis, perhaps analogous to cell reprogramming. Furthermore, FoxA and GATA factors are involved in a variety of hormone-dependent cancers, such as estrogen receptor-positive breast cancer and androgen receptor-positive prostate cancer (Zaret and Carroll 2011;Jozwik and Carroll 2012). In breast cancer, FoxA1 expression is a significant predictor of cancer-specific survival in patients (Badve et al 2007).…”

Section: Pioneer Factors In Disease Progressionmentioning

confidence: 99%

“…Chromatin decompaction Fakhouri et al 2010 Mitotic bookmarking (human) Binding to mitotic chromatin Caravaca et al 2013 Hormone-dependent cancer progression (human) Recruitment of hormone receptor Zaret and Carroll 2011;Jozwik and Carroll 2012 In vitro reconstituted nucleosome or nucleosome array…”

Section: Updike and Mango 2006mentioning

confidence: 99%

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Pioneer transcription factors in cell reprogramming

2014

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A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in ''closed'' chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as ''pioneer factors'' to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.Cell fate control represents the most extreme form of gene regulation. Genes specific to the function of a particular type of cell may be antagonistic to the function of another type of cell, so nature has evolved diverse regulatory mechanisms to ensure stable patterns of gene activation and repression. In prokaryotes, self-sustaining regulatory networks of transcription factors bound to DNA can be sufficient to regulate gene activation and repression (Ptashne 2011). In eukaryotes, ;200-base-pair (bp) segments of the genome are wound nearly twice around an octamer of the four core histones to form nucleosomes, providing steric constraints on how transcription factors can bind DNA (Kornberg and Lorch 1999). As described below, pioneer transcription factors have the special property of being able to overcome such constraints, enabling the factors to engage closed chromatin that is not accessible by other types of transcription factors (Fig. 1). However, further higher-order packaging of nucleosomes into heterochromatin can occlude access to DNA altogether, presenting an additional barrier to cell fate conversion (Fig. 1). This review focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatinbinding properties, and facilitators and impediments to chromatin binding. We project that such knowledge will greatly aid future efforts to change the fates of cells at will for research, diagnostic, and therapeutic purposes.

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“…7 However, the nature and prevalence of FOXA1 mutations in prostate cancer has not been comprehensively studied. The present analyses have revealed that FOXA1 mutation occurs at a rate of 3%-4% among primary prostate cancer and CRPC cases.…”

mentioning

confidence: 99%