A tissue-specific enhancer in the rat-calcitonin/CGRP gene is active in both neural and endocrine cell types

The calcitonin gene related peptide (CGRP) gene is a complex transcription unit that is expressed in a highly restricted pattern in both the nervous system, particularly in sensory ganglia and brainstem, and in the thyroid C cells of the endocrine system, with tissue-specific alternative RNA processing events generating transcripts encoding either the hormone, calcitonin, or the neuropeptide, CGRP. This pattern of expression in neural and endocrine tissues raises the question whether similar or distinct genomic elements are responsible for activation in both neural and endocrine cell types. We have identified a complex enhancer element, located more than 1 kilobase 5' of the transcription initiation site of the calcitonin/CGRP gene that functions in cells of neuronal or C cell origin, but not in any other cell type tested. At least two complementary regulatory sequences are required for the function of the cell-specific enhancer.