Premium
CTCF Is Essential for Up‐Regulating Expression from the Amyloid Precursor Protein Promoter During Differentiation of Primary Hippocampal Neurons
Author(s) -
Yang Yaxiong,
Quitschke Wolfgang,
Vostrov Alexander A.,
Brewer Gregory J.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732286.x
Subject(s) - synaptogenesis , synaptophysin , ctcf , biology , hippocampal formation , amyloid precursor protein , transcription factor , microbiology and biotechnology , transfection , medicine , neuroscience , cell culture , gene , genetics , alzheimer's disease , immunohistochemistry , immunology , enhancer , disease
: The transcriptional mechanism underlying amyloid precursor protein (APP) regulation in primary neurons during development was investigated. We observed an approximately threefold elevation of APP mRNA levels in differentiating rat hippocampal neurons between day 1 and day 7 in culture and in rat brain hippocampi between embryonic day 18 and postnatal day 3. When an APP promoter construct extending to position ‐2,832 upstream from the main transcriptional start site was transfected into primary rat hippocampal neurons, promoter activity increased from day 1 until reaching a maximum on day 7 in culture. This increase in APP promoter activity was correlated more closely with the time course of expression of the synaptic vesicle protein synaptophysin, an indicator of synaptogenesis, than with neurofilament accumulation, an indicator of neuritogenesis. Transfection of 5′ APP promoter deletions and internal block mutations indicated that the CTCF binding domain designated APBβ was the primary contributor to the increase in APP promoter activity. Furthermore, the binding of transcription factor CTCF to the APBβ element increased approximately fivefold between day 1 and day 7, whereas the binding of USF to the APBα sequence increased only twofold. These results suggest that CTCF is pivotal for the up‐regulation of APP expression during synaptogenesis in primary neurons.