Syntaxin 1A Gene Is Negatively Regulated in a Cell/Tissue Specific Manner by YY1 Transcription Factor, Which Binds to the −183 to −137 Promoter Region Together with Gene Silencing Factors Including Histone Deacetylase
Open Access
- 23 January 2021
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 11 (2), 146
- https://doi.org/10.3390/biom11020146
Abstract
The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.Keywords
This publication has 24 references indexed in Scilit:
- Purification and characterization of transcription factorsMass Spectrometry Reviews, 2013
- A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 ResponseCell, 2010
- Membrane Fusion: Grappling with SNARE and SM ProteinsScience, 2009
- Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTipsNature Protocols, 2007
- SNAREs — engines for membrane fusionNature Reviews Molecular Cell Biology, 2006
- Regulation of Transcription Factor YY1 by Acetylation and DeacetylationMolecular and Cellular Biology, 2001
- The Polycomb Group Protein EED Interacts with YY1, and Both Proteins Induce Neural Tissue in XenopusEmbryosMolecular and Cellular Biology, 2001
- Mapping of the Human HPC-1/Syntaxin 1A Gene (STX1A) to Chromosome 7 Band q11.2Genomics, 1997
- Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300.Genes & Development, 1995
- Syntaxin: A Synaptic Protein Implicated in Docking of Synaptic Vesicles at Presynaptic Active ZonesScience, 1992