MIST1 - A NOVEL BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR EXHIBITS A DEVELOPMENTALLY-REGULATED EXPRESSION PATTERN

Basic helix-loop-helix (bHLH) proteins often belong to a family of tra nscription factors that bind to the DNA target sequence -CANNTG- (E-bo x) that is present in the promoter or enhancer regions of numerous dev elopmentally regulated genes. In this study, we report the isolation a nd initial characterization of a novel bHLH factor, termed Mist1, that was identified by virtue of its ability to interact with E-box regula tory elements in a yeast ''one-hybrid'' screening procedure. Northern analysis revealed that Mist1 transcripts are expressed in several adul t tissues, including stomach, liver, lung, and spleen but no expressio n is detected in the heart, brain, kidney, or testis. During mouse emb ryogenesis, Mist1 mRNA is first observed at E10.5 in the primitive gut and in the developing lung bud. Expression persists through E16.5 and remains restricted primarily to the epithelial lining. Mist1 also is detected in skeletal muscle tissues beginning at E12.5, persisting thr oughout all embryonic stages examined although in older embryos and in the adult expression becomes severely reduced. At later developmental times, Mist1 transcripts also are found in the pancreas, submandibula r gland, and adult spleen. As predicted, the Mist1 protein is nuclear and binds efficiently to E-box sites as a homodimer. Mist1 also is cap able of binding to E-box elements when complexed as a heterodimer with the widely expressed E-proteins, E12 and E47. Surprisingly, although Mist1 binds to E-boxes in vivo, the Mist1 protein lacks a functional t ranscription activation domain. These observations suggest that Mist1 may function as a unique regulator of gene expression in several diffe rent embryonic and postnatal cell lineages. (C) 1997 Academic Press.