RGD Reference Report - Transcription regulation mechanism of the syntaxin 1A gene via protein kinase A. - Rat Genome Database

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Transcription regulation mechanism of the syntaxin 1A gene via protein kinase A.

Authors: Nakayama, Takahiro  Akagawa, Kimio 
Citation: Nakayama T and Akagawa K, Biochem J. 2017 Jul 11;474(14):2465-2473. doi: 10.1042/BCJ20170249.
RGD ID: 13208603
Pubmed: PMID:28559304   (View Abstract at PubMed)
DOI: DOI:10.1042/BCJ20170249   (Journal Full-text)

Syntaxin 1A (Stx1a) is primarily involved in the docking of synaptic vesicles at active zones in neurons. Its gene is a TATA-less gene, with several transcription initiation sites, which is activated by the binding of Sp1 and acetylated histone H3 (H3) in the core promoter region (CPR) through the derepression of class I histone deacetylase (HDAC). In the present study, to clarify the factor characterizing Stx1a gene expression via the protein kinase A (PKA) pathway inducing the Stx1a mRNA, we investigated whether the epigenetic process is involved in the Stx1a gene transcription induced by PKA signaling. We found that the PKA activator forskolin induced Stx1a expression in non-neuronal cells, FRSK and 3Y1, which do not endogenously express Stx1a, unlike PC12. HDAC8 inhibition by shRNA knockdown and specific inhibitors induced Stx1a expression in FRSK. The PKA inhibitor H89 suppressed HDAC8-Ser39 phosphorylation, H3 acetylation and Stx1a induction by forskolin in FRSK cells. Finally, we also found that forskolin led to the dissociation of HDAC8-CPR interaction and the association of Sp1 and Ac-H3 to CPR in FRSK. The results of the current study suggest that forskolin phosphorylates HDAC8-Ser39 via the PKA pathway and increases histone H3 acetylation in cells expressing HDAC8, resulting in the induction of the Stx1a gene.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to forskolin  IDA 13208603 RGD 
negative regulation of gene expression  IMP 13208603Stx1aRGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chromatin binding  IDA 13208603 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac8  (histone deacetylase 8)


Additional Information