Cary Weinberger

Developmental and Hormonal Regulation of Neuroendocrine Gene Transcription

Publisher Summary The quantitative regulation of gene transcription during development and by hormones appears to require the interaction of specific rate-limiting transcriptional factors that bind to structurally distinct genomic sequences. The precise molecular mechanisms by which the binding of these trans-acting factors increases the rate of accurate transcriptional initiation remain unknown; however, it is clear that the regulatory cis-active regions can represent either simple or complex elements. In the case of heritable patterns of neuroendocrine expression, a combinatorial reaction of several sequences and their cognate transcription factors appears requisite for cell-specific gene transcription. The multi-factorial nature of this regulation provides the possibility for a more restricted pattern of gene expression than that exhibited by the cognate trans-acting transcription factors. In the case of the rat prolactin gene, three to five discrete factors may be required for the upstream enhancer function. Additional important cell-specific enhancers appear to be present in proximity to the promoter. By contrast, several regulatory cis-active elements, such as those that transfer hormone regulation, appear to bind a unique transcription factor, which may be sufficient for activation of gene transcription.

A Neural Thyroid Hormone Receptor Gene

One of the prominent questions surrounding tissue-specific gene activation is how a single hormone type such as thyroxine can have such diverse physiological effects. Generally, two mechanisms contribute to the particular variety of proteins synthesized either during development or in response to required physiological changes. On the one hand, specific DNA tertiary structure induced by associated nuclear proteins probably presets the transcriptional activity of target cell gene networks (1). An additional constraint is likely provided by hormones or growth factors mediating changing gene expression patterns (2). Each cell produces distinct receptor proteins which determine the effective response to hormonal stimulation. In this manner, both the ontogenetic history of a particular cell type and the hormone receptor field, or its distribution in specific cell types, limit the scope of induced proteins during animal development and homeostasis.