Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: Differential phenotype of the Zac1‐expressing cells during development

Valente, Tony; Junyent, Fèlix; Auladell, Carme

doi:10.1002/dvdy.20373

Cited by 62 publications

(51 citation statements)

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“…Given the shared role of Zac1 and p73 in neurodevelopment and differentiation (35)(36)(37), further experiments focused on the Zac1 coactivation of p73 and its relevance to the finetuning of p73 target genes. Zac1 strongly enhanced the p73-dependent activation of the p21 Cip1 and Apaf-1 promoter plasmids but did not influence the activation of another p73 target, mdm2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Zac1's antiproliferative actions in mesenchymal and neural progenitor/stem cells indicates its importance for cell fate and lineage decisions (36,37). Previous studies demonstrate that either monomeric or dimeric Zac1 binding to GC-rich palindromic elements or to GC-rich direct-and reverse-repeat elements (4,16,38) underlies the activation of the H19, Lit1, peroxisome proliferatoractivated receptor gamma, and CK14 target genes (1,3,16,39).…”

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confidence: 99%

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A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

Hoffmann

Spengler

2008

Molecular and Cellular Biology

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The generally accepted paradigm of transcription by regulated recruitment defines sequence-specific transcription factors and coactivators as separate categories that are distinguished by their abilities to bind DNA autonomously. The C 2 H 2 zinc finger protein Zac1, with an established role in canonical DNA binding, also acts as a coactivator. Commensurate with this function, p73, which is related to p53, is here shown to recruit Zac1, together with the coactivators p300 and PCAF, to the p21 Cip1 promoter during the differentiation of embryonic stem cells into neurons. In the absence of autonomous DNA binding, Zac1's zinc fingers stabilize the association of PCAF with p300, suggesting its scaffolding function. Furthermore, Zac1 regulates the affinities of PCAF substrates as well as the catalytic activities of PCAF to induce a selective switch in favor of histone H4 acetylation and thereby the efficient transcription of p21 Cip1 . These results are consistent with an authentic coactivator function of Zac1's C 2 H 2 zinc finger DNA-binding domain and suggest coactivation by sequencespecific transcription factors as a new facet of transcriptional control.The transcriptional activation of eukaryotic genes involves the regulated assembly of multiprotein complexes on enhancers and promoters (9,22,23). The specificity of this process is decisively controlled by sequence-specific DNA-binding transcription factors (henceforth termed "sequence-specific factors") which play a key role in interpreting and transmitting the information contained in the primary DNA sequence to the factors and cofactors that, in turn, mediate the synthesis of RNA transcripts from the DNA template.Sequence-specific factors typically contain a specific DNAbinding domain that directly contacts DNA, a multimerization domain that allows the formation of homo-or heteromultimers, and a transcription activation domain. The binding of sequencespecific factors to regulatory DNA elements, through which they are tethered to their correct location, is a prerequisite for gene regulation. This allows the positioning of the activation domain in the vicinity of the initiation complex and the subsequent recruitment of an active transcription complex (30). The sequential order of these events underlies the concept of gene activation via regulated recruitment (29).Sequence-specific factors that do not directly contact the basal transcription machinery often bind to different classes of interconnecting coregulators (for a minimal classification see reference 22).Among these, primary coactivators bind directly to sequence-specific factors and often contain relevant enzymatic activities that are necessary for changing chromatin structure from a quiescent state to one that permits active gene transcription; prototypical examples are the coactivators p300/CBP and PCAF, which are endowed with potent histone acetyltransferase (HAT) activities (21). In contrast, secondary coactivators dock onto sequence-specific factors and form a scaffold, thus facilitating the recruitm...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

Hoffmann

Spengler

2008

Molecular and Cellular Biology

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“…All of these mRNAs encode for proteins with proliferative properties, which are down-regulated after injection of anti-NGF. On the other hand, PLAGL1, a known inhibitor of proliferation (46) that promotes apoptosis and cell cycle arrest in human cells (47,48), and the expression of which in neural tube and somites in mice (48) controls cell fate during neurogenesis, chondrogenesis, and myogenesis (49), is up-regulated after injection of anti-NGF.…”

Section: Discussionmentioning

confidence: 99%

Nerve growth factor regulates axial rotation during early stages of chick embryo development

Manca

Capsoni²,

Luzio³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Nerve growth factor (NGF) was discovered because of its neurotrophic actions on sympathetic and sensory neurons in the developing chicken embryo. NGF was subsequently found to influence and regulate the function of many neuronal and non neuronal cells in adult organisms. Little is known, however, about the possible actions of NGF during early embryonic stages. However, mRNAs encoding for NGF and its receptors TrkA and p75 NTR are expressed at very early stages of avian embryo development, before the nervous system is formed. The question, therefore, arises as to what might be the functions of NGF in early chicken embryo development, before its well-established actions on the developing sympathetic and sensory neurons. To investigate possible roles of NGF in the earliest stages of development, stage HH 11-12 chicken embryos were injected with an anti-NGF antibody (mAb αD11) that binds mature NGF with high affinity. Treatment with anti-NGF, but not with a control antibody, led to a dose-dependent inversion of the direction of axial rotation. This effect of altered rotation after anti NGF injection was associated with an increased cell death in somites. Concurrently, a microarray mRNA expression analysis revealed that NGF neutralization affects the expression of genes linked to the regulation of development or cell proliferation. These results reveal a role for NGF in early chicken embryo development and, in particular, in the regulation of somite survival and axial rotation, a crucial developmental process linked to left-right asymmetry specification.neurotrophins | rotatin | csk | furin | proNGF

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“…Zac1/Lot1 is abundantly expressed in many proliferative/differentiation areas during brain development (Valente and Auladel, 2001;Valente et al, 2005). Lot1-specific immunostaining was observed at postnatal Days 2-7 in the superficial external granule layer composed primarily of proliferating neuronal precursor cells .…”

Section: Gene Expression During Developmentmentioning

confidence: 99%

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

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Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: Differential phenotype of the Zac1‐expressing cells during development

Cited by 62 publications

References 62 publications

A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

Nerve growth factor regulates axial rotation during early stages of chick embryo development

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

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Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: Differential phenotype of the Zac1‐expressing cells during development

Cited by 62 publications

References 62 publications

A New Coactivator Function for Zac1's C2H2 Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

A New Coactivator Function for Zac1's C2H2 Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

Nerve growth factor regulates axial rotation during early stages of chick embryo development

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

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A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity

A New Coactivator Function for Zac1's C₂H₂ Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity