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. 2017 Apr 3;8:57. doi: 10.3389/fendo.2017.00057

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Copyright © 2017 Stefan and Faustino.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Thyroid-stimulating hormone receptor (TSHR) intron 1 Graves’ disease (GD)-associated DNA variants. (A) Schematic representation of the TSHR gene and the intron 1 GD-associated single nucleotide polymorphisms (SNPs). Black squares represent exons; white bars represent introns; white triangles in intron 1 represent the SNPs associated with GD susceptibility; gray bar overlapping the rs12101255 and rs12101261 represent the region characterized by H3K4me1 enrichment (47). (B) Proposed model for rs12101261 allele-dependent regulation of TSHR transcription. Upper panel: the presence of the disease-protective genotype (C/C) at the rs12101261 site prevents strong interactions with promyelocytic leukemia zinc finger protein (PLZF), allowing TSHR transcription; lower panel: the presence of the disease-associated genotype (T/T) facilitates binding of PLZF, triggering chromatin folding and interaction with TSHR promoter and transcriptional machinery.