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- Title
The cell- and tissue-specific transcription mechanism of the TATA-less syntaxin 1A gene.
- Authors
Takahiro Nakayama; Katsuhiko Mikoshiba; Kimio Akagawa
- Abstract
Syntaxin 1A (Stx1a) plays an important role in regulation of neuronal synaptic function. To clarify the mechanism of basic transcriptional regulation and neuronspecific transcription of Stx1a we cloned the Stx1a gene from rat, in which knowledge of the expression profile was accumulated, and elucidated that Stx1a consisting of 10 exons, possesses multiple transcription initiation sites and a 204-bp core promoter region (CPR) essential for transcription inPC12 cells. The TATA-less, conserved,GC-rich CPR has 2 specific protein (SP) sites that bind SP1 and are responsible for 65% of promoter activity. The endogenous CPR, including 23 CpG sites, is not methylated in PC12 cells, which express Stx1a and fetal rat skin keratinocyte (FRSK) cells, which do not, although an exogenous methylated CPR suppresses reporter activity in both lines. TrichostatinA(TSA)and class I histone deacetylase (HDAC) inhibitors, but not 5-azacytidine, induce Stx1a in FRSK cells. Acetylated histone H3 only associates to the CPR in FRSKcells after TSAaddition, where as the high acetylated histoneH3-CPR association in PC12 cells was unchanged following treatment. HDAC inhibitor induction of Stx1a was negated by mithramycin A and deletion/mutation of 2 SP sites. HDAC1, HDAC2, and HDAC8 detach from the CPR when treated with TSA in FRSK cells and are associated with the CPR in lungs, and acetylated histone H3 associates to this region in the brain. In the first study characterizing a syntaxin promoter, we show that association of SP1 and acetylated histoneH3 toCPR is important for Stx1a transcription and that HDAC1, HDAC2, and HDAC8 decide cell/tissue specificity in a suppressive manner.
- Subjects
TRANSCRIPTION factors; SYNTAXINS; BRAIN function localization; NEURONS; EXONS (Genetics); PROMOTERS (Genetics)
- Publication
FASEB Journal, 2016, Vol 30, Issue 2, p525
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.15-275529