FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription

Lupien, Mathieu; Eeckhoute, Jérôme; Meyer, Clifford A.; Wang, Qianben; Zhang, Yong; Li, Wei; Carroll, Jason S.; Liu, X. Shirley; Brown, Myles

doi:10.1016/j.cell.2008.01.018

Cited by 897 publications

(1,066 citation statements)

References 53 publications

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“…However, another study showed that reduction of H3K4me1 and H3K4me2 impaired FoxA binding in the breast cancer cell line MCF7 (Lupien et al 2008). Altogether, it appears that active histone modifications may enhance pioneer factor binding to chromatin but are not necessarily required for the factor's initial engagement.…”

Section: Positive Chromatin Features For Pioneer Factor Bindingmentioning

confidence: 99%

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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Section: Positive Chromatin Features For Pioneer Factor Bindingmentioning

confidence: 99%

Pioneer transcription factors in cell reprogramming

2014

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“…FOX family transcription factors influence ERα-regulated transcription by interaction with the ERα protein, as exemplified by FOXA1 [3]. Recent genome-wide studies aimed at identifying ERα and androgen receptor (AR) binding sites have shown that FOXA1 plays a role in regulating both of these nuclear receptor networks [4,5]. FOXA1 is recognized as a pioneer transcription factor because chromatin binding by this protein can enable subsequent binding by the estrogen and androgen receptors [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Recent genome-wide studies aimed at identifying ERα and androgen receptor (AR) binding sites have shown that FOXA1 plays a role in regulating both of these nuclear receptor networks [4,5]. FOXA1 is recognized as a pioneer transcription factor because chromatin binding by this protein can enable subsequent binding by the estrogen and androgen receptors [5,6]. Of other FOX family members, FKHR (also known as FOXO1A) also binds directly to ERα and increases its transactivation through an estrogen response element [7].…”

Section: Introductionmentioning

confidence: 99%

FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

et al. 2011

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Breast cancer is primarily a hormone-dependent tumor that can be regulated by the status of steroid hormones, including estrogen and progesterone. Forkhead box P1 (FOXP1) is a member of the forkhead box transcription factor family and has been reported to be associated with various types of tumors. In the present study, we investigated the expression of FOXP1 in 133 human invasive breast cancers, obtained by core biopsy, by immunohistochemical analysis. Nuclear immunoreactivity of FOXP1 was detected in 89 cases (67%) and correlated positively with tumor grade and hormone receptor status, including estrogen receptor alpha (ERα) and progesterone receptor, and negatively with pathological tumor size. In ERα-positive MCF-7 breast cancer cells, we demonstrated that FOXP1 mRNA was upregulated by estrogen and increased ERα recruitment to ER binding sites identified by ChIP-on-chip analysis within the FOXP1 gene region. We also demonstrated that proliferation of MCF-7 cells was increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA. Furthermore, FOXP1 enhanced estrogen response element-driven transcription in MCF-7 cells. Finally, FOXP1 immunoreactivity was sig-

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“…Ces changements épigénomiques résument donc la perte de différenciation observée dans les cellules cancéreuses. Les enhancers dirigent, via la modulation de l'expression des gènes, le phéno-type cellulaire [6][7][8]. Ainsi, l'acquisition ou la perte de ces éléments devrait se traduire par l'altération du programme transcriptionnel normal.…”

Section: Resultsunclassified

“…De plus, l'acétylation de la lysine 27 de l'histone H3 (H3K27ac) est associée à l'activité de ces éléments régulateurs [6,7]. La comparaison de la localisation de cette signature chromatinienne dans différents types cellulaires a permis de confirmer la nature spécifique des enhancers pour une cellule donnée [6][7][8]. Ceux-ci sont donc le déterminant majeur de l'expression du programme transcriptionnel responsable de B. Akhtar-Zaidi et al [1] révèlent que ces SNP, enrichis dans des régions enhancers marquées par H3K4me1 et spécifiques aux cellules de la crypte, sont détectés dans des régions de VEL acquis ou perdus dans les cellules CCR.…”

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