Pioneer transcription factors: establishing competence for gene expression

In the paper

“By these criteria, FoxA and GATA are initial and important chromatin-binding factors, and as such were termed pioneer factors.”

In the paper

“GATA-4 and GATA-6 are redundantly expressed in the foregut endoderm and are necessary for early liver development (Holtzinger and Evans 2005;Zhao et al. 2005;Watt et al. 2007).”

What the sources say

• Not checked yetcites Holtzinger and Evans 2005
• Not checked yetcites Zhao et al. 2005
• Not checked yetcites Watt et al. 2007

In the paper

“FoxA1 and FoxA2 are redundantly expressed in the foregut endoderm and are necessary for liver induction (Lee et al. 2005).”

What the sources say

• Not checked yetcites Lee et al. 2005

In the paper

“The importance of cooperative binding is reflected by the observation that many transcription factors individually cannot occupy their target sites on nucleosomal DNA in vitro, but cooperative interactions among a group of such factors can allow nucleosome binding (Adams and Workman 1995;Steger and Workman 1997).”

What the sources say

• Not checked yetcites Adams and Workman 1995
• Not checked yetcites Steger and Workman 1997

In the paper

“To summarize, many or most regulatory regions do not coincide with DNA sequence that assembles into intrinsically unstable nucleosomes.Thus, other mechanisms are needed to expose the DNA.”

In the paper

“Tuteja et al. (2008) did find that medium-and lower-affinity, liver-specific targets were highly enriched for binding of other hepatic nuclear factors, suggesting a role for cooperative binding during the maintenance of differentiation.”

What the sources say

• Not checked yetcites Tuteja et al. 2008

In the paper

“A distinction about the designation of pioneer factors is that they not only perform a genetic function early in the activation of transcription, but they have been physically shown to bind to the genome for a period prior to activation and prior to other factors binding and, as such, impart competence for activity (Fig. 1).”

In the paper

“However, all of the above observations do not address how general coregulators, chromatin modifiers, histone modifications, and hypersensitivity become localized to genomic sites in the first place and thus fail to resolve the issue of how regulatory events are initiated at particular genomic locations.”

In the paper

“While the specific dimethyl sulfate protection technique used for in vivo footprinting could have failed to detect other factors, FoxA and GATA site occupancy clearly preceded occupancy of the other enhancer-binding factors in nascent liver and occurred in progenitor cells prior to gene activation.”

What the sources say

• Not checked yetcites Gualdi et al. 1996

In the paper

“The binding sites were for FoxA and GATA factors, which are expressed in the endoderm and nascent liver (Ang et al. 1993;Arceci et al. 1993;Monaghan et al. 1993;Laverriere et al. 1994) and whose binding sites are crucial for Alb1 enhancer function (Liu et al. 1991;Bossard and Zaret 1998).”

What the sources say

• Not checked yetcites Ang et al. 1993
• Not checked yetcites Arceci et al. 1993
• Not checked yetcites Liu et al. 1991

In the paper

“genome-wide location analyses have revealed that, for all transcription factors tested, the vast majority of potential DNA-binding sites are unoccupied, demonstrating the inaccessibility of most of the nuclear DNA.”

In the paper

“With regard to FoxA1, a C-terminal domain of the protein, independent of the central, DNA-binding domain, binds to core histones and is necessary for chromatin opening in vitro (Cirillo et al. 2002).”

What the sources say

• Not checked yetcites Cirillo et al. 2002

In the paper

“While the two factors together are also not necessary for late fetal hepatocyte differentiation (Li et al. 2009), they are absolutely essential for the embryonic initiation of hepatic differentiation (Lee et al. 2005).”

What the sources say

• Not checked yetcites Li et al. 2009
• Not checked yetcites Lee et al. 2005

In the paper

“The FoxA factor was more active than the GATA factor in this regard, and studies of FoxE and FoxO have shown that they can similarly open compacted chromatin (Cuesta et al. 2007;Hatta and Cirillo 2007).”

What the sources say

• Not checked yetcites Cuesta et al. 2007
• Not checked yetcites Hatta and Cirillo 2007

In the paper

“Chromatin opening properties have also been seen for the basic helix-loop-helix (bHLH) factor TFE3, which, in vitro, induces hypersensitivity in chromatin and mediates local nucleosome positioning (Ishii et al. 2004).”

What the sources say

• Not checked yetcites Ishii et al. 2004

In the paper

“PU.1 and RUNX1 prime transcription of the c-fms/ csf1R gene, with RUNX1 being needed only transiently (Krysinska et al. 2007;Hoogenkamp et al. 2009).”

What the sources say

• Not checked yetcites Krysinska et al. 2007
• Not checked yetcites Hoogenkamp et al. 2009

In the paper

“Also, like linker histone, FoxA and other Fox family members are retained on mitotic chromosomes and thus could serve as ''bookmarking'' proteins in mitosis (Yan et al. 2006;Zaret et al. 2011).”

What the sources say

• Not checked yetcites Yan et al. 2006
• Not checked yetcites Zaret et al. 2011

In the paper

“For example, direct assessments of FoxA1 and GATA-4, in comparison with other Alb1 enhancer-binding proteins, showed that these pioneer factors were uniquely capable of binding to their target sites in highly compacted chromatin in vitro and generating a local region of DNase or restriction enzyme sensitivity (Cirillo et al. 2002).”

What the sources say

• Not checked yetcites Cirillo et al. 2002

In the paper

“In conclusion, the structure of the FoxA DNA-binding domain appears intermediate between that of linker histone and other transcription factors, and this feature contributes to pioneer activity.”

In the paper

“Also, from the fetal stages onward, a third homolog, FoxA3, is expressed in the liver and apparently provides compensation ( Z Li et al. 2011).”

What the sources say

• Not checked yetcites Z Li et al. 2011

In the paper

“An example of this is at the aforementioned Alb1 enhancer, where FoxA and GATA factor sites are bound in the endoderm, allowing a rapid and synchronous transcriptional response in the cell population receiving liver-inductive signals.”

In the paper

“Indeed, FoxA proteins can bind their target sites on a nucleosome core particle in vitro and in vivo, and the DNA-binding domain alone is sufficient for such binding (Cirillo et al. 1998;Chaya et al. 2001).”

What the sources say

• Not checked yetcites Cirillo et al. 1998
• Not checked yetcites Chaya et al. 2001

In the paper

“While FoxA factors lack the requisite basic residues on the ''back'' side of the globular domain to enable such binding, conversion of analogously positioned residues to basic residues in FoxA enables the factor to bind nucleosomes more tightly, similar to linker histone (Cirillo et al. 1998).”

What the sources say

• Not checked yetcites Cirillo et al. 1998

In the paper

“Notably, FoxA proteins move in nuclear chromatin much more slowly than other factors tested, implicating unusually tight chromatin binding in vivo (Sekiya et al. 2009).”

What the sources say

• Not checked yetcites Sekiya et al. 2009

In the paper

“Notably, FoxD3 was shown to block methylation of an underlying CpG sequence at the silent Alb1 gene in ES cells, demonstrating that pioneer factor occupancy can modulate the local epigenetic state of chromatin (Xu et al. 2009).”

What the sources say

• Not checked yetcites Xu et al. 2009

In the paper

“The rate of association of FoxA for nucleosomes is low, apparently due to the need for proper rotational phasing of the target site on the nucleosome surface (Sekiya et al. 2009), but the rate of dissociation is much lower than that for free DNA (Cirillo and Zaret 1999).”

What the sources say

• Not checked yetcites Sekiya et al. 2009
• Not checked yetcites Cirillo and Zaret 1999

In the paper

“PU.1 itself can expand the linker region between nucleosomes and promote local histone modifications, likely contributing to its ability to enhance binding of other factors (Ghisletti et al. 2010;Heinz et al. 2010).”

What the sources say

• Not checked yetcites Ghisletti et al. 2010
• Not checked yetcites Heinz et al. 2010

In the paper

“While the FoxA factors have base-specific contacts with DNA that are necessary for site-specific binding (Clark et al. 1993;Sekiya et al. 2009), linker histone lacks such contacts and does not bind DNA sites specifically.”

What the sources say

• Not checked yetcites Clark et al. 1993
• Not checked yetcites Sekiya et al. 2009

In the paper

“Thus, binding of FoxA1 can help stabilize a nucleosome position (Shim et al. 1998), which in turn can phase other local binding sites on and off of nucleosomes to modulate factor binding.”

What the sources say

• Not checked yetcites Shim et al. 1998

In the paper

“Interestingly, while Grg3 tetramers by themselves avidly bind chromatin, they do not elicit closing, herein defined as conferring resistance to nuclease access (Sekiya and Zaret 2007).”

What the sources say

• Not checked yetcites Sekiya and Zaret 2007

In the paper

“Undifferentiated embryonic endoderm cells express Grg1 and Grg3 when the albumin gene is silent, and both Grgs are markedly down-regulated during hepatic specification when the albumin gene is activated (Santisteban et al. 2010).”

What the sources say

• Not checked yetcites Santisteban et al. 2010

In the paper

“The yeast Rap1 protein can bind target sites in chromatin and open the domain for other factors (Yu and Morse 1999;Koerber et al. 2009).”

What the sources say

• Not checked yetcites Yu and Morse 1999
• Not checked yetcites Koerber et al. 2009

In the paper

“Pioneer factors can thus actively help initiate the assembly of regulatory factors on the DNA by either opening the chromatin locally, positioning nucleosomes, enabling intrinsic cooperative binding effects among other DNA-binding factors, or directly recruiting other chromatin modifiers and coregulators.”

In the paper

“Taken together, it appears that FoxA may recruit a corepressor to maintain the silent, competent state, and loss of the corepressor contributes to activation that is enabled by FoxA and additional factors that bind the enhancer during liver induction (Gualdi et al. 1996).”

What the sources say

• Not checked yetcites Gualdi et al. 1996

In the paper

“The yeast Gal4 protein's DNA-binding domain can bind nucleosomal DNA in vitro and in vivo, the latter without replication, and stabilize distinct nucleosome positions (Taylor et al. 1991;Pazin et al. 1998;Balasubramanian and Morse 1999).”

What the sources say

• Not checked yetcites Taylor et al. 1991
• Not checked yetcites Pazin et al. 1998
• Not checked yetcites Balasubramanian and Morse 1999

In the paper

“ER is a member of the nuclear hormone receptor family of transcription factors, a subset of which, including the androgen receptor (AR) and the GR, is not stably bound to chromatin in unstimulated cells”

What the sources say

• Not checked yetcites Glass and Rosenfeld 2000
• Not checked yetcites Hager et al. 2004

In the paper

“Finally, FoxA proteins have an N-terminal, trans-activation domain (Fig. 3; Pani et al. 1992) that presumably recruits coregulators, which in turn can facilitate other factors to enter the chromatin.”

What the sources say

• Not checked yetcites Pani et al. 1992

In the paper

“FoxA1 binding is required for genes that are either induced or repressed by ER, as well as for ER binding in the presence of both an agonist (estrogen) and an antagonist (tamoxifen)”

What the sources say

• Not checked yetcites Malik et al. 2010
• Not checked yetcites Hurtado et al. 2011

In the paper

“Although such target sequences may be a minority for GR at the genomic level (John et al. 2011), the sites where GR induces hypersensitivity are where other factors can subsequently enter the chromatin and therefore represent regions where GR serves as a pioneer factor (Voss et al. 2011).”

What the sources say

• Not checked yetcites John et al. 2011
• Not checked yetcites Voss et al. 2011

In the paper

“The dependency of significant ER binding on FoxA1 illustrates that the latter functions as a pioneer factor for ER in breast cancer cells.”

In the paper

“ER can positively regulate FoxA1 expression (and that of GATA3)”

What the sources say

• Not checked yetcites Laganiere et al. 2005

In the paper

“expression of FoxA1 in ER-negative cells results in opportunistic binding of FoxA1 to numerous regions lacking H3K4me1 or H3K4me2 marks, followed by subsequent methylation of these histone residues”

What the sources say

• Not checked yetcites Serandour et al. 2011

In the paper

“its expression negatively correlates with tumor grade and is associated with better survival”

What the sources say

• Not checked yetcites Laganiere et al. 2005
• Not checked yetcites Thorat et al. 2008
• Not checked yetcites Albergaria et al. 2009

In the paper

“we conclude that there are defined features of chromatin that can facilitate FoxA1 binding in breast cancer cells”

In the paper

“Specific silencing of FoxA1 decreases the hypersensitivity of specific ER-and FoxA1-binding regions without affecting H3K4me1 or H3K4me2 levels”

What the sources say

• Not checked yetcites Lupien et al. 2008

In the paper

“;1 million predicted EREs exist in the human genome”

What the sources say

• Not checked yetcites Vega et al. 2006
• Not checked yetcites Joseph et al. 2010

In the paper

“FoxA1 both positively and negatively regulates AR-binding potential”

In the paper

“implying that the presence of the H3K4me1 and H3K4me2 marks is important for FoxA1 binding (Lupien et al. 2008) and, therefore, ER binding”

In the paper

“Expression of FoxA1 in U20S-ER cells can induce ER binding to regions previously only observed in the breast cancer cells, and this alters the genes that estrogen-ER can transcribe”

What the sources say

• Not checked yetcites Hurtado et al. 2011

In the paper

“A role for FoxA1 as a nuclear receptor regulatory protein and pioneer factor is not limited to ER and appears to be a more general phenomenon observed for other hormoneresponsive nuclear receptors.”

In the paper

“Molecular apocrine breast cancers are ER À AR + but express a gene expression pattern resembling an ER + breast cancer”

What the sources say

• Not checked yetcites Farmer et al. 2005
• Not checked yetcites Doane et al. 2006

In the paper

“heavily methylated regions may negatively impact ERand/or FoxA1-binding potential”

In the paper

“This establishes a stable platform for recruitment of ER-associated cofactors and mediating chromatin loops with promoters of target genes.”

In the paper

“Upon FoxA1 binding, chromatin condensation is relieved further, thereby allowing ER to bind to local EREs”

In the paper

“In molecular apocrine breast cancer cells, AR substitutes for ER and uses FoxA1 to bind to the regulatory regions normally occupied by ER”

What the sources say

• Not checked yetcites Ni et al. 2011
• Not checked yetcites Robinson et al. 2011

In the paper

“it is possible that their accompanying pioneer factors may constitute therapeutic targets”

What the sources say

• Not checked yetcites Nakshatri and Badve 2007
• Not checked yetcites Fu et al. 2011
• Not checked yetcites Hurtado et al. 2011

In the paper

“GATA proteins can bind to condensed chromatin and can induce local nuclease hypersensitivity, albeit more weakly than that by FoxA1”

What the sources say

• Not checked yetcites Cirillo et al. 2002

In the paper

“the emerging picture involves multiple pioneer factors that contribute to ER-chromatin interactions, with an interplay and dependency existing between the factors”

In the paper

“ER binding is redirected to different regions in the genome (Krum et al. 2008), and this is mediated by GATA4”

What the sources say

• Not checked yetcites Krum et al. 2008
• Not checked yetcites Miranda-Carboni et al. 2011

In the paper

“In many of the gene transduction studies, multiple factors are required for the cellular conversion, and in cases in which a single ectopic factor has been used, it converts cells from related germ layer lineages.”

In the paper

“FoxA factors still bind chromatin sites when other factors cannot, and enable other factors to bind”

In the paper

“is essential for ER-mediated transcription of target genes and for growth of MCF-7 breast cancer cells”

What the sources say

• Not checked yetcites Eeckhoute et al. 2007

In the paper

“Pioneer factors, including FoxA proteins, can initiate such regulatory events, at least in part due to their resemblance to linker histone, and, hence, special nucleosome-and chromatinbinding properties”

In the paper

“Specific silencing of FoxA1 inhibits the proliferation of tamoxifen-resistant MCF-7 cells”

What the sources say

• Not checked yetcites Hurtado et al. 2011
• Not checked yetcites Yamaguchi et al. 2008

In the paper

“GATA motifs are also enriched in AR-binding events in LnCaP prostate cancer cells, and GATA2 is shown to be recruited to several AR-binding regions, where it is required for effective AR-chromatin interactions”

What the sources say

• Not checked yetcites Wang et al. 2007

In the paper

“genes can exist in stable states where they are transcriptionally silent, yet competent for expression”

In the paper

“there are numerous genomic sites where such ''pioneer'' binding creates local hypersensitivity and promotes the recruitment of other transcription factors”

What the sources say

• Not checked yetcites Voss et al. 2011

In the paper

“While FoxA binding to target sequences on nucleosomes is efficient in vitro with unmodified histones, in vivo the factor exhibits preferences for particular modified domains”

In the paper

“Following FoxA1 and GR recruitment to the MMTV promoter, associated transcription factors, including NF1 and Oct1, can get recruited and increase transcriptional activity, but this can be dependent on the presence of FoxA1”

What the sources say

• Not checked yetcites Belikov et al. 2009

In the paper

“AP-2g binds to a significant fraction of ER-binding events, where it is essential for estrogenmediated transcription and ER binding”

What the sources say

• Not checked yetcites Tan et al. 2011

In the paper

“GATA3 is required for mammary gland development (Asselin-Labat et al. 2007) and maintains cellular differentiation in the adult”

What the sources say

• Not checked yetcites Asselin-Labat et al. 2007
• Not checked yetcites Kouros-Mehr et al. 2006

In the paper

“Increasing the number of cell divisions during reprogramming increases the time for stochastic events to occur, and thus enhances reprogramming efficiency”

What the sources say

• Not checked yetcites Hanna et al. 2009

In the paper

“Only a small subset of the targeted cells becomes converted, suggesting that either a subset of the cells are competent or stochastic parameters are involved”

What the sources say

• Not checked yetcites Yamanaka 2009