NGF‐dependent and tissue‐specific transcription of <i>vgf</i> is regulated by a CREB–p300 and bHLH factor interaction

Mandolesi, Georgia; Gargano, Silvia; Pennuto, Maria; Illi, Barbara; Molfetta, Rosa; Soucek, Laura; Mosca, Laura; Levi, Andrea; Jucker, Richard; Nasi, Sergio

doi:10.1016/s0014-5793(01)03227-6

Cited by 24 publications

(12 citation statements)

References 31 publications

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“…Nonetheless, NGF has minimal ability to activate CREB-mediated gene transcription (52)(53)(54) as well as P2X 3 gene expression in TG neurons (22). In the present investigation, BDNF was an intermediate of the CGRP-induced events and was, per se, an adequate stimulus for P2X 3 gene transcription in TG neurons as much as CGRP itself.…”

Section: Molecular Elements Involved In P2x 3 Gene Transcriptionmentioning

confidence: 44%

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Simonetti

Giniatullin

Fabbretti

2008

Journal of Biological Chemistry

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The molecular mechanisms underlying migraine pain remain unclear and probably require sustained facilitation in pain-sensing P2X 3 receptors gated by extracellular ATP in nociceptive sensory neurons. The major migraine mediator calcitonin generelated peptide (CGRP) is known to sensitize P2X 3 receptors to increase impulse flow to brainstem trigeminal nuclei. This process is mediated via changes in the expression and function of P2X 3 receptors initially through enhanced trafficking and, later, perhaps through augmented synthesis of P2X 3 receptors. To clarify the mechanisms responsible for CGRP-evoked long lasting alterations in P2X 3 receptors, we used as a model mouse trigeminal ganglion neurons in culture. CGRP activated Ca 2؉ -calmodulin-dependent kinase II, which became localized to the perimembrane region and neuronal processes, a phenomenon already apparent after 30 min and accompanied by a parallel increase in cAMP-response element-binding protein (CREB) phosphorylation and nuclear translocation. These effects triggered increased P2X 3 receptor transcription and were prevented by expressing a dominant negative form of CREB. Increased P2X 3 receptor synthesis was partly mediated by endogenous brain-derived neurotrophic factor (BDNF) because of its block by anti-BDNF antibodies and mimicry by exogenous BDNF. Immunocytochemistry experiments indicated distinct subpopulations of BDNF-or CGRP-sensitive trigeminal neurons with only partial overlap. The present data indicate a novel mechanism for enhancing P2X 3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation. BDNF was an intermediate to extend the sensitizing effect of CGRP also to CGRP-insensitive neurons. This combinatorial action could serve as a powerful process to amplify and prolong pain mediated by P2X 3 receptors.Sensitization of sensory neurons represents the key phenomenon for generating chronic pain that remains relatively refractory to standard treatment (1). Current theories predict that chronic pain is brought about by a gain in the expression and function of sensory nociceptors that enhance their signal flow to the brain to ensure the long lasting nature of this process (2). Clarification of the novel gene expression profiles associated to pain should, therefore, be useful to target emerging molecules (and mechanisms) and for designing new analgesics. Previous studies (3) aimed at detecting changes in transcriptome patterns during pain conditions have provided only a limited description of the global alterations because of the complexity of pain pathologies and signal pathways.Migraine is a classical example of chronic, relapsing pain triggered by local release of endogenous pain mediators, such as the neuropeptide calcitonin gene-related peptide (CGRP) 2 (4, 5) that induces long lasting trigeminal neuronal sensitization (6) and novel gene transcription in sensory neurons (7-9). CGRPmediated signals are transduced at the cell membrane by activation of a G-protein-coupled receptor complex (composed b...

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Section: Molecular Elements Involved In P2x 3 Gene Transcriptionmentioning

confidence: 44%

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Simonetti

Giniatullin

Fabbretti

2008

Journal of Biological Chemistry

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“…A number of studies have demonstrated that HEB is able to function both as an activator and a repressor on a given promoter, depending on the presence of other factors (31,45,54). In particular, HEB represses activation of the GAP-43 gene in PC12 cells, pending expression of Nex1/MATH2, a member of the neuroD family of bHLH factors (50).…”

Section: Discussionmentioning

confidence: 99%

MyoD Synergizes with the E-Protein HEBβ To Induce Myogenic Differentiation

Parker

Perry

Fauteux³

et al. 2006

Molecular and Cellular Biology

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The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate ␣ and ␤ isoforms. While the function of these molecules has been studied in other cell types, questions persist regarding the molecular functions of HEB proteins in skeletal muscle. Our data demonstrate that HEB␣ expression remains unchanged in both myoblasts and myotubes, whereas HEB␤ is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEB␤ complex bound the E1 E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEB␤ with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEB␣ and HEB␤ synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEB␤ by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEB␣ and HEB␤ play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation.Basic helix-loop-helix (bHLH)-containing transcription factors play an important role in directing the development of a variety of cellular lineages by regulating expression of a restricted set of tissue-specific target genes (57). The myogenic regulatory factors (MRFs) are a group of muscle-specific bHLH transcription factors, consisting of MyoD, Myf5, myogenin, and MRF4, that control skeletal muscle development (41). Genetic and expression analyses indicate that Myf5 and MyoD act as determination factors that specify muscle progenitor cell identity. Although expression of MyoD or Myf5 commits a cell to the myogenic lineage, expression of MyoD is more effective at initiating differentiation. Myogenin is induced upon differentiation and plays an important role in activating the differentiation program. MRF4 appears to have a role as a determination factor in a subset of myocytes in the early somite and as a differentiation factor in later muscle fibers (24).Transcription of muscle-specific genes is dependent upon dimer interactions between MRFs and the more ubiquitously expressed E-proteins, a process mediated by the helix-loophelix motif. The E-protein family includes the E2A gene products (E12/E47), the E2-2 gene products (ITF-2A and 2B), and the HEB gene products (HEB␣ and HEB␤). Dimerization is dependent upon the relative abundance of each transcription factor and/or the presence of other factors that may potentiate or inhibit dimerization. Therefore, the ability of bHLH factors to homo-or heterodimerize in a variety of combinations raises the hypothesis that regulation of dimer formation is essential for control of muscle-specific gene expression.The role of E2A in myogenesis was first postulated upon finding that MyoD was able to heterodimerize with E12 and E47 in vitro (34, 35)....

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“…The promoter regions of some other genes were shown to possess juxtaposed or overlapping CRE and E box elements. The cooperativity between their respective binding factors could be either positive, as for the follicle-stimulating hormone-mediated activation of the transferrin promoter (16) or for the mouse renin promoter (67), negative, as for the cholecystokinin gene promoter (70) or for the macrophage cyclooxygenase-2 promoter (60), or context dependent, as for the vgf gene promoter (53). In the BLV promoter, the CRE consensus within the three TxREs is never strictly conserved in any viral strain.…”

Section: Discussionmentioning

confidence: 99%

Overlapping CRE and E Box Motifs in the Enhancer Sequences of the Bovine Leukemia Virus 5′ Long Terminal Repeat Are Critical for Basal and Acetylation-Dependent Transcriptional Activity of the Viral Promoter: Implications for Viral Latency

Calomme

Dekoninck

Nizet

et al. 2004

J Virol

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Bovine leukemia virus (BLV) infection is characterized by viral latency in a largeIn the course of retrovirus infection, the integration of the viral DNA into the host genome is a crucial step in the virus life cycle. This step is important for the efficient expression of progeny virus and is responsible for the ability of retroviruses to persist and cause disease (72). Once integrated, the proviral DNA is organized into chromatin, as are all cellular genes. At least two different, yet highly conserved, mechanisms are at work to alter chromatin structure: chromatin remodeling activities and/or factors and posttranslational modifications of histone proteins, in particular, histone acetylation (reviewed in references 46 and 63). Acetylation of histones allows DNA to become more accessible to the transcriptional machinery and can lead to nucleosome disruption. In contrast, histone deacetylation allows the histones to bind more tightly to DNA and therefore contributes to a transcriptionally repressed chromatin architecture. The level of histone acetylation is determined by the competition between enzymatic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) (18). The activity of a de novo integrated retroviral promoter can be strongly affected by the site of integration and by the histone acetylation status at this site.Previous reports have demonstrated that deacetylases play an important role in transcriptional silencing of several viruses, such as Epstein-Barr virus (EBV) (37, 77), human cytomegalovirus (57), and Kaposi's sarcoma-associated herpesvirus (29). Regarding retroviruses, feline foamy virus was shown to be reactivated following deacetylase inhibitor treatment (32) and histone hyperacetylation induces human immunodeficiency virus type 1 expression by specifically disrupting a single nucleosome positioned immediately downstream of the transcription start site (20,33,83). The presence of HDACs in the human T-cell leukemia virus type 1 (HTLV-1) promoter was recently observed, and treatment of HTLV-1-infected cells with deacetylase inhibitors increases the level of histone H4 acetylation in the HTLV-1 promoter and concomitantly increases viral transcription (48).Bovine leukemia virus (BLV) gene expression is induced at the transcriptional level by the virus-encoded transactivator

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NGF‐dependent and tissue‐specific transcription of vgf is regulated by a CREB–p300 and bHLH factor interaction

Cited by 24 publications

References 31 publications

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

MyoD Synergizes with the E-Protein HEBβ To Induce Myogenic Differentiation

Overlapping CRE and E Box Motifs in the Enhancer Sequences of the Bovine Leukemia Virus 5′ Long Terminal Repeat Are Critical for Basal and Acetylation-Dependent Transcriptional Activity of the Viral Promoter: Implications for Viral Latency

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