PBX1 as Pioneer Factor: A Case Still Open

Grebbin, Britta Moyo; Schulte, Dorothea

doi:10.3389/fcell.2017.00009

Cited by 43 publications

(35 citation statements)

References 70 publications

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“…This would indicate that, in this context, TALEs access promoters during early embryogenesis, facilitating chromatin accessibility of transcriptionally inactive genes, but Hox proteins are subsequently required to initiate transcription (Choe et al 2014). Accordingly, it was proposed that during early development, PBX proteins can mark genes for transcriptional activation as part of multimeric complexes, suggesting their potential roles as "pioneer factors" (for review, see Grebbin and Schulte 2017). However, a currently held definition of pioneer factors specifies that their binding to a DNA element is not dependent on pre-existing histone modifications that are indicative of gene activation (for reviews, see Iwafuchi-Doi and Zaret 2014;Donaghey et al 2018).…”

Section: Partnerships Of Pbc Tfsmentioning

confidence: 99%

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

2019

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Pbx genes encode transcription factors that belong to the TALE (three-amino-acid loop extension) superclass of homeodomain proteins. We have witnessed a surge in information about the roles of this gene family as leading actors in the transcriptional control of development. PBX proteins represent a clear example of how transcription factors can regulate developmental processes by combinatorial properties, acting within multimeric complexes to implement activation or repression of transcription depending on their interaction partners. Here, we revisit long-emphasized functions of PBX transcription factors as cofactors for HOX proteins, major architects of the body plan. We further discuss new knowledge on roles of PBX proteins in different developmental contexts as upstream regulators of Hox genes-as factors that interact with non-HOX proteins and can work independently of HOX-as well as potential pioneer factors. Committed to building a perfect body, PBX proteins govern regulatory networks that direct essential morphogenetic processes and organogenesis in vertebrate development. Perturbations of PBX-dependent networks can cause human congenital disease and cancer.

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Section: Partnerships Of Pbc Tfsmentioning

confidence: 99%

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

2019

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“…Recently, it has also been noted that PBX1 may act as a pioneer transcription factor, which is a type of transcription factor that can recognize and bind to their target sites even when chromatin is tightly wound rather than loose and easily accessible (Donaghey et al, 2018; Grebbin & Schulte, 2017). Few pioneer factors have been identified and thoroughly studied, but evidence from in vivo and in vitro studies suggests that PBX1 might belong to this category.…”

Section: Genetic Networkmentioning

confidence: 99%

“…Few pioneer factors have been identified and thoroughly studied, but evidence from in vivo and in vitro studies suggests that PBX1 might belong to this category. The three hallmarks of pioneer factor function reside in: (a) binding to target sites in closed chromatin, (b) increasing DNA access for other proteins, and (c) being actively involved in cell fate specification or cellular (re)programming (Grebbin & Schulte, 2017; Iwafuchi-Doi & Zaret, 2016). With respect to (a), it has been shown that PBX1 binds to target sites in promoter/enhancer regions of genes such as Dcx and Th before they become transcriptionally active, suggesting that PBX1 target sites for these genes could be located in closed chromatin at the time of binding (Brill et al, 2008; Grebbin & Schulte, 2017).…”

Section: Genetic Networkmentioning

confidence: 99%

Genetics of scapula and pelvis development: An evolutionary perspective

Young

Selleri

Capellini

2019

Current Topics in Developmental Biology

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In tetrapods, the scapular and pelvic girdles perform the important function of anchoring the limbs to the trunk of the body and facilitating the movement of each appendage. This shared function, however, is one of relatively few similarities between the scapula and pelvis, which have significantly different morphologies, evolutionary histories, embryonic origins, and underlying genetic pathways. The scapula evolved in jawless fish prior to the pelvis, and its embryonic development is unique among bones in that it is derived from multiple progenitor cell populations, including the dermomyotome, somatopleure, and neural crest. Conversely, the pelvis evolved several million years later in jawed fish, and it develops from an embryonic somatopleuric cell population. The genetic networks controlling the formation of the pelvis and scapula also share similarities and differences, with a number of genes shaping only one or the other, while other gene products such as PBX transcription factors act as hierarchical developmental regulators of both girdle structures. Here, we provide a detailed review of the cellular processes and genetic networks underlying pelvis and scapula formation in tetrapods, while also highlighting unanswered questions about girdle evolution and development.

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“…Studies in zebrafish and mouse embryos, as well as in mammalian cell culture models, have shown that Pbx proteins bind with Myod1 on the promoters of a subset of Myod1 target genes, including Myog and mylpfa (Berkes et al, 2004;Cho et al, 2015;de la Serna et al, 2005;Dell'Orso et al, 2016;Heidt et al, 2007;Maves et al, 2007;Pliner et al, 2018). Pbx proteins can bind silent Myod1 target gene promoters prior to Myod1 binding and muscle differentiation, suggesting the potential for Pbx proteins to function as pioneer factors in skeletal muscle differentiation (Berkes et al, 2004;Cho et al, 2015;de la Serna et al, 2005;Dell'Orso et al, 2016; for discussion of Pbx proteins as pioneer factors, see Schulte, 2017 andSelleri et al, 2019). Pbx genes are broadly expressed during embryogenesis and are required for many aspects of mouse embryo development (reviewed in Moens and Selleri, 2006;and Selleri et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

Farr¹,

Risolino

et al. 2020

Preprint

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Vertebrate skeletal muscles are composed of both slow-twitch and fast-twitch fiber types. How the differentiation of distinct fiber types is activated during embryogenesis is not well characterized. Skeletal muscle differentiation is initiated by the activity of the myogenic basic helix-loop-helix (bHLH) transcription factors Myf5, Myod1, Myf6, and Myog. Myod1 functions as a muscle master regulatory factor and directly activates muscle differentiation genes, including those specific to both slow and fast muscle fibers. Our previous studies showed that Pbx TALE-class homeodomain proteins bind with Myod1 on the promoter of the zebrafish fast muscle gene mylpfa and are required for proper activation of mylpfa expression and the fasttwitch muscle-specific differentiation program in zebrafish embryos. Pbx proteins have also been shown to bind regulatory regions of muscle differentiation genes in mammalian muscle cells in culture. Here, we use new zebrafish mutant strains to confirm the essential roles of zebrafish Pbx factors in embryonic fast muscle differentiation. Furthermore, we examine the requirements for Pbx genes in mouse embryonic skeletal muscle differentiation, an area that has not been investigated in the mammalian embryo. Removing Pbx1 function from skeletal muscle in Myf5 Cre/+; Pbx1 fl/fl mouse embryos has minor effects on embryonic muscle development.However, concomitantly deleting Pbx2 function in Myf5 Cre/+ ;Pbx1 fl/fl ;Pbx2 -/mouse embryos causes delayed activation and reduced expression of fast muscle differentiation genes. In the mouse, Pbx1/Pbx2-dependent fast muscle genes closely match those that have been previously shown to be dependent on murine Six1 and Six4. This work establishes evolutionarily conserved requirements for Pbx factors in embryonic fast muscle differentiation. Our studies are revealing how Pbx homeodomain proteins help direct specific cellular differentiation pathways.

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PBX1 as Pioneer Factor: A Case Still Open

Cited by 43 publications

References 70 publications

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

Genetics of scapula and pelvis development: An evolutionary perspective

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

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