Paired‐Like Homeodomain Proteins, Phox2a and Phox2b, Are Responsible for Noradrenergic Cell‐Specific Transcription of the Dopamine β‐Hydroxylase Gene

• Published in: Journal of neurochemistry 1998-11, Vol.71 (5), p.1813-1826
• Main Authors: Yang, Chunying, Kim, Hee‐Sun, Seo, Hyemyung, Kim, Chun‐Hyung, Brunet, Jean‐Francois, Kim, Kwang‐Soo
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites - physiology; Biological and medical sciences; Cell‐type specific transcription; cis‐acting element; Dopamine beta-Hydroxylase - genetics; Dopamine beta-Hydroxylase - metabolism; Dopamine β‐hydroxylase; Fundamental and applied biological sciences. Psychology; Homeodomain protein; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeodomain Proteins - physiology; Humans; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation - genetics; Nerve Tissue Proteins; Neurons - physiology; Noradrenergic neuron; Norepinephrine - physiology; Phox2a; Phox2b; Promoter Regions, Genetic - genetics; Rats; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Transcription, Genetic - physiology; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation - physiology; Tumor Cells, Cultured
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.71051813.x

: Recently, a murine paired‐like homeobox gene, Phox2a, has been identified whose product is critical for the development of several major noradrenergic neuron populations, including the locus coeruleus. In noradrenergic neurons, dopamine β‐hydroxylase (DBH) is a hallmark protein and catalyzes the conversion of dopamine to noradrenaline. Our previous studies have shown that a composite promoter (domain IV), residing at −185 to −150 bp upstream of the transcription start site, is critical for DBH transcription and is comprised of multiple cis‐acting elements, including a cyclic AMP response element, a YY1 binding site, and two core motifs of the homeodomain (HD)‐binding site. Here, we show that the HD‐binding site residing within domain IV is a noradrenergic‐specific cis‐acting element. In contrast, the cyclic AMP response element is active in all cell lines tested. We provide evidence that Phox2a is expressed only in DBH‐positive cell lines and interacts with the HD‐binding site. Forced expression of Phox2a robustly activates DBH promoter activity in DBH‐negative cell lines (>10‐fold), but increased it only marginally (