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Article: Identification of a Smad4/YY1-recognized and BMP2-responsive transcriptional regulatory module in the promoter of mouse GABA transporter subtype I (Gat1) gene

TitleIdentification of a Smad4/YY1-recognized and BMP2-responsive transcriptional regulatory module in the promoter of mouse GABA transporter subtype I (Gat1) gene
Authors
Issue Date2010
PublisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org
Citation
Journal of Neuroscience, 2010, v. 30 n. 11, p. 4062-4071 How to Cite?
AbstractGABAergic dysfunction is implicated in a variety of neurodevelopmental and psychiatric disorders. The mechanisms underlying GABAergic differentiation, however, are not well understood. GABA transporter 1 (Gat1; Slc6a1) is an essential component of the GABAergic system, and its ectopic mRNA expression may be responsible for GABAergic malfunction under different pathological conditions. Thus, monitoring the transcriptional regulation of gat1 may help to elucidate the mechanisms that govern the differentiation of GABAergic neurons. In this study, we identified a promoter region that is sufficient to recapitulate endogenous gat1 expression in transgenic mice. A 46 bp cis-regulator in the promoter sequence was responsible for the stimulation of bone morphogenetic protein-2 (BMP2) on gat1 expression in cortical cortex. Furthermore, our study demonstrated that Smad4 and YY1 are physically bound to the element and mediate both the negative and positive regulatory effects in which BMP2 can affect the balance. In summary, we have identified a Smad4/YY1-based bidirectional regulation model for GABAergic gene transcription and demonstrated a molecular cue important for the differentiation of GABAergic neurons.
Persistent Identifierhttp://hdl.handle.net/10722/124510
ISSN
2015 Impact Factor: 5.924
2015 SCImago Journal Rankings: 5.105
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30670438
National Key Basic Research Program2002CB713803
National High Technology Research and Development Program2008AA02Z126
Science and Technology Commission of Shanghai Municipality07DZ19503, 06DZ19004
E-Institutes of Shanghai Municipal Education CommissionE03003
Funding Information:

This work was supported by grants from the National Natural Science Foundation of China (30670438), the National Key Basic Research Program (2002CB713803), the National High Technology Research and Development Program (2008AA02Z126), the Science and Technology Commission of Shanghai Municipality (07DZ19503, 06DZ19004), and E-Institutes of Shanghai Municipal Education Commission (E03003). We are grateful to Dr. Fang Huang, Dr. Mei Yu, and Jiajuan Shen for technical assistance, and Dr. Kehong Zhang from Ivy Editing for language editing. We thank Xixia Zhou for animal care.

 

DC FieldValueLanguage
dc.contributor.authorYao, Men_HK
dc.contributor.authorNiu, Gen_HK
dc.contributor.authorSheng, Zen_HK
dc.contributor.authorWang, Zen_HK
dc.contributor.authorFei, Jen_HK
dc.date.accessioned2010-10-31T10:38:29Z-
dc.date.available2010-10-31T10:38:29Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal of Neuroscience, 2010, v. 30 n. 11, p. 4062-4071en_HK
dc.identifier.issn0270-6474-
dc.identifier.urihttp://hdl.handle.net/10722/124510-
dc.description.abstractGABAergic dysfunction is implicated in a variety of neurodevelopmental and psychiatric disorders. The mechanisms underlying GABAergic differentiation, however, are not well understood. GABA transporter 1 (Gat1; Slc6a1) is an essential component of the GABAergic system, and its ectopic mRNA expression may be responsible for GABAergic malfunction under different pathological conditions. Thus, monitoring the transcriptional regulation of gat1 may help to elucidate the mechanisms that govern the differentiation of GABAergic neurons. In this study, we identified a promoter region that is sufficient to recapitulate endogenous gat1 expression in transgenic mice. A 46 bp cis-regulator in the promoter sequence was responsible for the stimulation of bone morphogenetic protein-2 (BMP2) on gat1 expression in cortical cortex. Furthermore, our study demonstrated that Smad4 and YY1 are physically bound to the element and mediate both the negative and positive regulatory effects in which BMP2 can affect the balance. In summary, we have identified a Smad4/YY1-based bidirectional regulation model for GABAergic gene transcription and demonstrated a molecular cue important for the differentiation of GABAergic neurons.-
dc.languageengen_HK
dc.publisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org-
dc.relation.ispartofJournal of Neuroscienceen_HK
dc.rightsJournal of Neuroscience. Copyright © Society for Neuroscience.-
dc.subject.meshBone Morphogenetic Protein 2 - antagonists and inhibitors - biosynthesis - genetics-
dc.subject.meshGABA Plasma Membrane Transport Proteins - genetics - metabolism - physiology-
dc.subject.meshPromoter Regions, Genetic - physiology-
dc.subject.meshRegulatory Sequences, Nucleic Acid - genetics - physiology-
dc.subject.meshSmad4 Protein - genetics - metabolism - physiology-
dc.titleIdentification of a Smad4/YY1-recognized and BMP2-responsive transcriptional regulatory module in the promoter of mouse GABA transporter subtype I (Gat1) geneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-6474&volume=30&issue=11&spage=4062&epage=4071&date=2010&atitle=Identification+of+a+Smad4/YY1-recognized+and+BMP2-responsive+transcriptional+regulatory+module+in+the+promoter+of+mouse+GABA+transporter+subtype+I+(Gat1)+gene-
dc.identifier.emailNiu, G: wniu@hkucc.hku.hken_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1523/JNEUROSCI.2964-09.2010-
dc.identifier.pmid20237276-
dc.identifier.scopuseid_2-s2.0-77949697767-
dc.identifier.hkuros180104en_HK
dc.identifier.volume30en_HK
dc.identifier.issue11-
dc.identifier.spage4062en_HK
dc.identifier.epage4071-
dc.identifier.isiWOS:000275724800022-

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