Deficiency in the Transcription Factor GLIS3 Impairs Thyroid Follicular Cell Functions and Abrogates Goiter Development

Presentation Number: SUN 261
Date of Presentation: April 2nd, 2017

Hong Soon Kang*1, Kristin Lichti-kaiser1, Grace Liao1, Dhirendra Kumar1, Samuel Refetoff2, Raja Jothi1 and Anton M Jetten3
1NIH/NIEHS, RTP, NC, 2The University of Chicago, Chicago, IL, 3NIH/NIEHS, Research Triangle Pk, NC


Human genetic studies have indicated that deficiency in the Krüppel-like zinc finger transcription factor, GLI-similar 3 (GLIS3), leads to the development of congenital hypothyroidism. However, the function of Glis3 in the thyroid and hypothyroidism is not well understood. In this study, we demonstrate that in the thyroid Glis3 protein is restricted to the nucleus of thyroid follicular cells and that the serum as well as the thyroid levels of triiodothyronine (T3) and thyroxine (T4) mice were dramatically decreased, while serum TSH was significantly elevated in Glis3 knockout (Glis3KO) mice compared to wild type (WT) mice. In addition, in contrast to WT mice, Glis3KO mice did not develop goiter when fed a low iodine diet (LID). Gene expression profiling and EdU incorporation analysis demonstrated that proliferation of thyroid follicular cells was greatly reduced in Glis3KO mice, which was in part due to an impairment in the activation of the mTOR signaling pathway. Our gene expression analysis further showed that the expression of a set of genes associated with thyroid hormone biosynthesis, including NIS and pendrin, were greatly reduced in Glis3KO thyroids. ChIP-seq analyses indicated that Glis3 regulates the transcription of a number of these genes directly. Our study identifies Glis3 as a critical regulator of thyroid follicular cell proliferation, thyroid hormone production, and TSH signaling as well the development of goiter.


Nothing to Disclose: HSK, KL, GL, DK, SR, RJ, AMJ