LE-PAS, a novel Arnt-dependent HLH-PAS protein, is expressed in limbic tissues and transactivates the CNS midline enhancer element

Abstract

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.