The thyroid hormone-regulated corepressor hairless associates with histone deacetylases in neonatal rat brain

Abstract

Thyroid hormone (TH) influences multiple aspects of neural development, presumably by controlling the transcriptional activity of TH receptors to modulate gene expression. The mammalian hairless (hr) gene is likely an important component of TH action as 1) hr expression is directly regulated by TH in brain, and 2) the protein encoded by hr (Hr) acts as a corepressor, facilitating transcriptional repression by unliganded TH receptors. Here we examine the properties of endogenous Hr in developing rat brain. Using coimmunoprecipitation, we show that Hr interacts with TH receptor and histone deacetylases (HDACs) in brain extracts. We find that inhibition of HDAC activity impairs Hr-mediated transcriptional repression, indicating that Hr-HDAC interaction is functionally significant. To identify potential sites of Hr action in developing brain, we assessed hr transcript and protein expression. We show that hr is broadly expressed in brain and overlaps with the expression of multiple HDACs in multiple regions including cortex, hippocampus, and cerebellum. Additionally, Hr expression is TH sensitive and developmentally regulated. The striking correlation of Hr expression with brain regions, cell types, and developmental stages influenced by TH, together with its function as a corepressor, suggests Hr is a key mediator of TH action in developing brain.