The transcription factor Yin Yang 1 is an activator of BACE1 expression

• Published in: Journal of neurochemistry Vol. 96; no. 6; pp. 1696 - 1707
• Main Authors: Nowak, Katrin, Lange‐Dohna, Christine, Zeitschel, Ulrike, Günther, Albrecht, Lüscher, Bernhard, Robitzki, Andrea, Perez‐Polo, Regino, Roßner, Steffen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-03-2006; Blackwell; Blackwell Publishing Ltd
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - biosynthesis; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases; Animals; Animals, Newborn; Aspartic Acid Endopeptidases; Astrocytes - metabolism; BACE1 promoter; Binding Sites - genetics; Biological and medical sciences; Brain - metabolism; Brain - physiopathology; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Endocrinopathies; Endopeptidases - genetics; Endopeptidases - metabolism; Enzymes; Gene expression; Gene Expression Regulation - genetics; gliosis; Gliosis - genetics; Gliosis - metabolism; Humans; Medical sciences; Neurology; Neurons - metabolism; Non tumoral diseases. Target tissue resistance. Benign neoplasms; PC12 Cells; Peptides; Plaque, Amyloid - genetics; Plaque, Amyloid - metabolism; primary cultures; Promoter Regions, Genetic - genetics; Protein Binding - genetics; Rats; Rats, Inbred SHR; Regulatory Elements, Transcriptional - genetics; Transcriptional Activation - genetics; transcriptional regulation; Yin Yang 1; YY1 Transcription Factor - genetics; YY1 Transcription Factor - metabolism; Endocrinopathy; Pheochromocytoma; Peptides; Rat; Alzheimer disease; Neuroglia; primary cultures; transcriptional regulation; Central nervous system; Secretory tumor; Enzymatic activity; Primary culture; Yin Yang 1; Degenerative disease; gliosis; Transcription factor; Glycine dehydrogenase (decarboxylating); Alzheimer's disease; Nervous system diseases; Enzyme; Rodentia; Astrocyte; Amyloid precursor protein; Cerebral disorder; Vertebrata; Mammalia; Neuron; Central nervous system disease; Oxidoreductases; BACE1 promoter
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.03692.x

The β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β‐amyloid peptides, the principle constituents of senile plaques in the brains of patients with Alzheimer's disease (AD). BACE1 expression and enzymatic activity are increased in the AD brain, but the regulatory mechanisms of BACE1 expression are largely unknown. Here we show that Yin Yang 1 (YY1), a highly conserved and multifunctional transcription factor, binds to its putative recognition sequence within the BACE1 promoter and stimulates BACE1 promoter activity in rat pheochromocytoma 12 (PC12) cells, rat primary neurones and astrocytes. In rat brain YY1 and BACE1 are widely expressed by neurons, but there was only a minor proportion of neurones that co‐expressed YY1 and BACE1, suggesting that YY1 is not required for constitutive neuronal BACE1 expression. Resting astrocytes in the untreated rat brain did not display either YY1 or BACE1 immunoreactivity. When chronically activated, however, astrocytes expressed both YY1 and BACE1 proteins, indicating that YY1 is important for the stimulated BACE1 expression by reactive astrocytes. This is further emphasized by the expression of YY1 and BACE1 by reactive astrocytes in proximity to β‐amyloid plaques in the AD brain. Our observations suggest that interfering with expression, translocation or binding of YY1 to its BACE1 promoter‐specific sequence may have therapeutic potential for treating patients with AD.