Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.

Chavrier, Philippe; Janssen-Timmen, U.; Mattei, Marie-Genevı̀eve; Zerial, Marino; Bravo, Rodrigo; Charnay, Patrick

doi:10.1128/mcb.9.2.787

Cited by 141 publications

(59 citation statements)

References 69 publications

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“…5 gene induced by LSD is krox-20, which encodes for a zinc finger transcription factor. Krox-20 contains a c-fos serum response element in its promoter region, suggesting that it is co-regulated with c-fos (Chavrier et al 1989). Krox-20 has been shown to be necessary for normal brain development (Seitanidou et al 1997) and may be involved in the maintenance of long-term potentiation (Inokuchi et al 1996).…”

Section: Discussionmentioning

confidence: 99%

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

Nichols

Sanders‐Bush

2002

Neuropsychopharmacology

139

100

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Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including INTRODUCTIONLysergic acid diethylamide (LSD) is an hallucinogenic drug that transiently but powerfully alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia (Breier 1995). Despite extensive research over the past four decades, the mechanism of action of hallucinogenic drugs still largely remains a mystery. The behavioral effects of LSD are believed to arise in part from agonist activity at the 5-HT 2A , 5-HT 2C , and 5-HT 1A receptor subtypes (Burris et al. 1991; KrebsThomson et al. 1998;Titeler et al. 1988), but if, and how, these interactions affect cognitive functions remains unknown. In addition to actions at serotonin receptors, LSD has high affinity for dopamine receptors and has been shown to act as an agonist at these receptors (Giacomelli et al. 1998;Watts et al. 1995). Because LSD is a unique ligand that can simultaneously bind to serotonin and dopamine receptor subtypes implicated in both normal and abnormal human behaviors, it is an excellent tool for probing the biochemical basis for behavior.Simply increasing brain levels of serotonin, however, does not produce hallucinogenic effects. Recent work has demonstrated that while LSD binds to the same re- NO . 5 LSD-influenced Gene Expression 635 ceptor sites as the endogenous ligand serotonin, it has the capacity to activate different intracellular signaling cascades (Backstrom et al. 1999). Because intracellular signaling cascades influence gene expression, LSDinduced signaling events within cells may inappropriately alter gene expression, which in turn may lead to changes in the physiological status of the neurons, ultimately altering the processes of cognition. Certain behavioral effects of LSD resemble paranoid schizophrenia in humans. This particular subset of mood alterations occurs within the "second phase . . . of the LSD experience" as defined by Freedman, and may be specific for LSD (Freedman 1984). These delayed "second phase" effects could result from transient changes in gene expression. Thus, identifying and characterizing these genes could prove to be important in understanding mechanisms underlying how hallucinogens such as LSD alter behavior. In addition, understanding these mechanisms may lead to the identification of novel therapeutic targets for treatment of mental disorders.We took a broad approach to investigating and identifying genes that are altered by an acute dose of LSD in the mammalian brain. First, we investigated the expression of the mRNAs of the 5-HT receptor subtypes thought to mediate hallucinogenic effects in animal models (5-HT 1A,2A,2C ), as well as, specific gene expression of immediate early genes predicted to be affected by LSD. Next, we performed a DNA microarray screen to identify gene expression influenced by LSD at a more global level. For each gene identified,...

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Section: Discussionmentioning

confidence: 99%

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

Nichols

Sanders‐Bush

2002

Neuropsychopharmacology

139

100

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“…Taken together, these results provide a functional link between activation of ERKs and regulation of glutamateinduced neuronal gene expression. Because some glutamateregulated immediate early genes (IEGs) such as Zif268 and Krox 20 are also induced by LTP paradigms, and SREs are present within the promoters of these IEGs (Changelian et al, 1989;Chavrier et al, 1989;Christy and Nathans, 1989), the mechanisms described here for the regulation of c-fos SRE transcription may be used generally by neurons to regulate gene expression during LTP and other adaptive neuronal responses.…”

Section: Discussionmentioning

confidence: 99%

Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK-Dependent Mechanism

et al. 1996

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The regulation of gene expression by neurotransmitters is likely to play a key role in neuroplasticity both during development and in the adult animal. Therefore, it is important to determine the mechanisms of neuronal gene regulation to understand fully the mechanisms of learning, memory, and other long-term adaptive changes in neurons. The neurotransmitter glutamate stimulates rapid and transient induction of many genes, including the c-fos proto-oncogene. The c-fos promoter contains several critical regulatory elements, including the serum response element (SRE), that mediate glutamate-induced transcription in neurons; however, the mechanism by which the SRE functions in neurons has not been defined. In this study, we sought to identify transcription factors that mediate glutamate induction of transcription through the SRE in cortical neurons and to elucidate the mechanism(s) of transcriptional activation by these factors. To facilitate this analysis, we developed an improved calcium phosphate coprecipitation procedure to transiently introduce DNA into primary neurons, both efficiently and consistently. Using this protocol, we demonstrate that the transcription factors serum response factor (SRF) and Elk-1 can mediate glutamate induction of transcription through the SRE in cortical neurons. There are at least two distinct pathways by which glutamate signals through the SRE: an SRF-dependent pathway that can operate in the absence of Elk and an Elk-dependent pathway. Activation of the Elkdependent pathway of transcription seems to require phosphorylation of Elk-1 by extracellular signal-regulated kinases (ERKs), providing evidence for a physiological function of ERKs in glutamate signaling in neurons. Taken together, these findings suggest that SRF, Elk, and ERKs may have important roles in neuroplasticity.

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“…SRF was ®rst identi®ed based on its ability to mediate serum and growth factor activation of the c-fos proto-oncogene (reviewed in Treisman and Ammerer, 1992). Subsequently, it was found that SRF and/or SRF binding sites (CC(A/ T) 6 GG), termed CArG boxes, regulate expression of a wide variety of serum responsive genes (Changelian et al, 1989;Chavrier et al, 1989;Christy and Nathans, 1989;Latinkic et al, 1991;Latinkic and Lau, 1994;Treisman, 1990;Tsai-Morris et al, 1988). SRF also regulates transcription mediated by treatment of cells with neurotrophins (Sheng et al, 1988;Visvader et al, 1988), neurotransmitters and agents that raise intracellular calcium levels (Bading et al, 1993;McDonough et al, 1997;Misra et al, 1994), stress agents, and viral activators (Avantaggiati et al, 1993;Fujii et al, 1992Fujii et al, , 1994.…”

Section: Introductionmentioning

confidence: 99%

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Spencer

Misra

1999

Oncogene

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Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.

Cited by 141 publications

References 69 publications

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK-Dependent Mechanism

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

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