Transcription Factors Regulating Neuroendocrine Development, Function, and Oncogenesis

Coulson, Judy M ORCID: 0000-0003-2191-2001 and Concannon, Matthew ORCID: 0000-0001-8777-4786 (2016) Transcription Factors Regulating Neuroendocrine Development, Function, and Oncogenesis. In: Molecular Neuroendocrinology: From Genome to Physiology. International Neuroendocrine Federation (INF) Masterclass Series . Wiley,., pp. 97-120. ISBN 9781118760376, 1118760379

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Abstract

Transcriptional regulation contributes to the hierarchy of processes that ensure proteins are expressed in the correct cells at appropriate times. Such exquisite control is critical for neurohormones, which are induced in response to specific physiological signals, and for which inappropriate expression has pathological consequences. The basal transcription of genes is modulated by the sequence-specific binding of transcription factors (TFs) to enhancer or repressor elements within the gene control regions. These TFs are modular proteins, which use specialized DNA-binding domains to interact at the correct DNA sequence motifs. Here they form scaffolds that recruit regulatory co-factors to modify the surrounding chromatin. The nature of these co-factors determines whether a TF functions as an activator or a repressor of transcription. Here we consider classes of TFs that regulate the expression of neuropeptides, drive the development of neuroendocrine tissues or define neuroendocrine cancers. Genome-wide studies are now beginning to reveal the extent and diversity of the binding motifs for individual TFs. Many TFs regulate transcription of messenger RNAs and also non-coding RNAs, which themselves exert transcriptional or posttranscriptional regulation of gene expression. The regulation of TFs by alternative splicing, posttranslational modifications, protein-protein interactions, and subcellular relocalization also diversifies their function. TFs often contribute to cascades of transcriptional regulators or work in feedback loops. Thus transcriptional regulation is complex, cooperative and dynamic, relying on the integration of signals generated by multiple TFs to determine the transcriptional output of a given gene. This chapter discusses these themes and some of the experimental techniques used to study the regulation and function of TFs, highlighting specific neuroendocrine-associated examples. Thus, we focus on (i) the diversity of function for REST, a TF with roles in neuroendocrine physiology and oncogenesis, (ii) the transcriptional cascades that drive development of the hypothalamic-pituitary axis, and (iii) context-dependent TF function at the gene promoter for the neuropeptide arginine vasopressin (AVP).

Item Type:	Book Section
Uncontrolled Keywords:	Medical
Depositing User:	Symplectic Admin
Date Deposited:	21 Aug 2017 10:50
Last Modified:	05 Sep 2023 02:31
DOI:	10.1002/9781118760369.ch5
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3004551