Pbx Marks Genes for Activation by MyoD Indicating a Role for a Homeodomain Protein in Establishing Myogenic Potential

Berkes, Charlotte A.; Bergstrom, Donald A.; Penn, Bennett H.; Seaver, Karen J.; Knoepfler, Paul S.; Tapscott, Stephen J.

doi:10.1016/s1097-2765(04)00260-6

Cited by 309 publications

(400 citation statements)

References 48 publications

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“…The synergism between Arx, Mef2C and MyoD could result from a specific recognition event between the multiprotein complex and a component of the transcriptional machinery or it could result from a concerted reaction in which the assembly of the three factors stabilizes a transcriptional complex, similarly to what was reported for MyoD and Pbx, the latter containing a homeodomain like Arx. 28 The data presented here also show that Arx and Myogenin can upregulate each other's expression. Similarly, Mef2 gene products also regulate Myogenin expression 9,29 and the Mef2 genes are known targets of the myogenic basic helix-loophelix (bHLH) (24).…”

Section: Discussionsupporting

confidence: 64%

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Biressi

Messina²,

Collombat

et al. 2007

Cell Death Differ

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Skeletal muscle fibers form in overlapping, but distinct phases that depend on the generation of temporally different lineages of myogenic cells. During primary myogenesis (E10.5-E12.5 in the mouse), embryonic myoblasts fuse homotypically to generate primary fibers, whereas during later development (E14.5-E17.5), fetal myoblasts differentiate into secondary fibers. How these myogenic waves are regulated remains largely unknown. Studies have been hampered by the lack of markers which would distinguish embryonic from fetal myoblast populations. We show here that the homeobox gene Arx is strongly expressed in differentiating embryonic muscle, downstream of myogenic basic helix-loop-helix (bHLH) genes. Its expression progressively decreases during development. When overexpressed in the C2C12 myogenic cell line, Arx enhances differentiation. Accordingly, it stimulates the transcriptional activity from the Myogenin promoter and from multimerized E-boxes when co-expressed with MyoD and Mef2C in CH310T1/2. Furthermore, Arx co-immunoprecipitates with Mef2C, suggesting that it participates in the transcriptional regulatory network acting in embryonic muscle. Finally, embryonic myoblasts isolated from Arx-deficient embryos show a delayed differentiation in vivo together with an enhanced clonogenic capacity in vitro. We propose here that Arx acts as a novel positive regulator of embryonic myogenesis by synergizing with Mef2C and MyoD and by establishing an activating loop with Myogenin.

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Section: Discussionsupporting

confidence: 64%

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Biressi

Messina²,

Collombat

et al. 2007

Cell Death Differ

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“…26 PBX1 is known to act as co-factor for MyoD as well as Hox. 27 Binding of PBX1 to the MyoD-dependent promoter occurs before MyoD binding, then muscle differentiation starts. 27 From these findings, it is postulated that PBX penetrates into condensed chromatin and changes the local condition from silent to active stage ready for binding of gene-specific transcription factor.…”

Section: Discussionmentioning

confidence: 99%

“…27 Binding of PBX1 to the MyoD-dependent promoter occurs before MyoD binding, then muscle differentiation starts. 27 From these findings, it is postulated that PBX penetrates into condensed chromatin and changes the local condition from silent to active stage ready for binding of gene-specific transcription factor. 27,28 The fluorescent immunohistochemical analysis showed the co-localization of PBX1 and VCP in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…27 From these findings, it is postulated that PBX penetrates into condensed chromatin and changes the local condition from silent to active stage ready for binding of gene-specific transcription factor. 27,28 The fluorescent immunohistochemical analysis showed the co-localization of PBX1 and VCP in the cytoplasm. PBX1 has two nuclear localization signals, which are masked by intramolecular interaction with the N terminus.…”

Section: Discussionmentioning

confidence: 99%

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Pre-B-Cell Leukemia Transcription Factor 1 Regulates Expression of Valosin-Containing Protein, a Gene Involved in Cancer Growth

Qiu

Tomita

Zhang

et al. 2007

The American Journal of Pathology

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Valosin-containing protein (VCP) is involved in a wide variety of cellular functions. Our previous studies showed that the enhanced expression of VCP in cancer cells correlated with invasion and metastasis of cancers. Here, the regulatory mechanism for VCP transcription was investigated. Luciferase reporter constructs containing serially deleted 5 -flanking region of the VCP gene were transfected into MCF7 mammary carcinoma cell line, in which VCP was abundantly expressed. The deletion and mutation at the two binding motifs for pre-B-cell leukemia transcription factor 1 (PBX1) reduced the luciferase activity, indicating that these two PBX1 motifs medi- Valosin-containing protein (VCP, or p97), a member of the ATPases associated with various cellular activities (AAA) superfamily, is essential for a wide variety of cellular functions such as ubiquitin/proteasome-dependent protein degradation, membrane fusion, cell cycle regulation, and endoplasmic reticulum-associated degradation. 1-5 Notably, VCP is involved in activation of nuclear factor (NF)-B, a transcription factor promoting antiapoptosis, cell proliferation, and invasion. 6 VCP is abundant in all kinds of cells, accounting for more than 1% of total cellular protein. 1 Recently, we showed that VCP is associated with metastatic potential of murine osteosarcoma cell line by using mRNA subtraction technique: the cell lines transfected with VCP showed the constant activation of NF-B, decreased apoptosis rates after stimulation with tumor necrosis factor (TNF)-␣, and increased metastatic potential. 7 Subsequent studies on the clinical samples showed that the high level of VCP expression in cancer cells correlated with the increase in recurrence rate and poor prognosis of patients with cancer of the liver, stomach, prostate, colorectum, pancreas, esophagus, and lung. 8 -14 A clear correlation in VCP expression between mRNA and protein levels was found, indicating that the up-regulation of VCP transcription resulted in the enhanced VCP expression in cancers, which is advantageous for cancer cells to survive and metastasize. 8,10,13 This implies that VCP transcription would be a novel target for cancer therapy.Previous study on the basal transcription activity of mouse VCP gene revealed the importance of the 410-bp sequence of the 5Ј-flanking region, which contains consensus binding sites for several transcription factors. 15 However, the precise mechanism for VCP transcription has not been clarified yet. No study has been done on the human VCP promoter. In the present study, 5Ј-flanking DNA sequence of the VCP gene in the human genome was analyzed, revealing the pre-B-cell leukemia transcription factor 1 (PBX1) to be a key factor for transcription of VCP.

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“…However, exogenous MyoD in endodermal and ectodermal cells failed to induce a full phenotypic switch (Weintraub et al 1989;Sch€ afer et al 1990). Later studies revealed that MyoD induces myogenin through cooperation with the Pbx factor, which is constitutively bound to MyoD target sites in fibroblasts prior to MyoD expression (Berkes et al 2004). There are many other examples of direct cell conversion within the same germ layer: the combination of PU.1 and C/EBPa into macrophage-like cells from fibroblasts (Feng et al 2008) and GATA4, MEF2C, TBX5, Hand2, and NKX2.5 for cardiomyocytelike cells from fibroblasts (Ieda et al 2010;Addis et al 2013).…”

Section: Espinosa and Emerson 2001mentioning

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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Pbx Marks Genes for Activation by MyoD Indicating a Role for a Homeodomain Protein in Establishing Myogenic Potential

Cited by 309 publications

References 48 publications

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Pre-B-Cell Leukemia Transcription Factor 1 Regulates Expression of Valosin-Containing Protein, a Gene Involved in Cancer Growth

Pioneer transcription factors in cell reprogramming

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