Conserved Upstream Regulatory Regions in Mammalian Tyrosine Hydroxylase

In this study, we examined the 11  kb upstream nucleotide sequence ofTh from nine mammalian species and identified five highly conserved regions. Using cultured human cells and mouse olfactory bulb tissue, chromatin immunoprecipitation (ChIP) assays show that these conserved regions recruit transcription factors that are established regulators ofTh transcription (such as NURR1, PITX3, FOXA2, MEIS2, and PAX6). This analysis also identified a conserved binding site for CTCF, and functional studies in cultured human cells and ChIP assays with mouse tissue show that CTCF is a novel regulator ofTh transcription in the forebrain. Together, the findings in this study provide key insights into the upstream regulatory genomic architecture and regulatory mechanisms controlling mammalianTh gene transcription.

Source: Molecular Neurobiology - February 5, 2018 Category: Neurology Source Type: research