LE-PAS, a novel Arnt-dependent HLH-PAS protein, is expressed in limbic tissues and transactivates the CNS midline enhancer element.
A growing family of helix-loop-helix PAS (HLH-PAS) transcription factors has emerged recently. These proteins form heterodimers and are involved in adaptation to environmental or physiologic stresses as well as in embryonic development. We describe the cloning and characterization of a novel HLH-PAS protein termed LE-PAS (limbic-enriched PAS) in mouse. LE-PAS consists of 802 amino acids and has a predicted molecular mass of 87.4 kDa. In adult mice, it is expressed exclusively in brain. Northern blot and in situ hybridization analysis indicate that LE-PAS is expressed in the limbic system and olfactory bulb. By in vitro overexpression in COS-7, cells we found that LE-PAS is a nuclear protein. Reporter gene analysis indicated that LE-PAS transactivates the CNS midline enhancer (CME) motif but not the xenobiotic response element in an Arnt-dependent fashion and without prior activation of LE-PAS protein. Our observation suggests that LE-PAS shares a similar mode of function with HLH-PAS proteins such as single minded or trachealess indicating that LE-PAS also has constitutive or developmental functions which may be critical for regulating the transcriptional control of limbic patterning and function.
Moser
Martin
M
Carolina Cardiovascular Biology Center, 103 Mason Farm Road, Glaxo Building Room 156, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7126, USA.
Knoth
Rolf
R
Bode
Christoph
C
Patterson
Cam
C
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D017403:In Situ Hybridization / Q000379:methods; D019476:Insect Proteins / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D019476:Insect Proteins; C495186:LE-PAS protein, mouse; D009419:Nerve Tissue Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator