Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors.
The regulatory region of the neuronal nicotinic acetylcholine (nACh) receptor alpha 2 subunit gene is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This pattern of regulation has not previously been observed for other neuronally expressed genes, several of which, such as those encoding alpha-internexin or SNAP-25, are activated by Brn-3a and Brn-3c but repressed by Brn-3b. The alpha 3 nACh receptor subunit gene is also shown to be activated by Brn-3a but is repressed by Brn-3b and Brn-3c. In contrast, the Brn-3 POU family transcription factors have no effects on either the alpha 7 or beta 4 nACh receptor subunit genes. The actions of Brn-3b on the alpha 2 subunit are thus in contrast to the inhibitory actions of Brn-3b on several promoters that are activated by Brn-3 alpha. The different actions of the Brn-3 POU factors on the range of nACh receptor genes tested suggests that the novel stimulation of the alpha 2 subunit by Brn-3b is specific to this subunit and not a general feature of nACh receptor genes.
Milton
N G
NG
Department of Molecular Pathology, University College London Medical School, UK.
Bessis
A
A
Changeux
J P
JP
Latchman
D S
DS
D000109:Acetylcholine; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000737:chemistry*; D050809:POU Domain Factors; D011401:Promoter Regions, Genetic; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050809:POU Domain Factors; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors; D000109:Acetylcholine