Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas

Koen M.A. Dreijerink , Radhika A. Varier , Rick van Nuland , Roel Broekhuizen , Gerlof D. Valk , Jacqueline E. van Der Wal , Cornelis J.M. Lips , J. Alain Kummer , H.Th. Marc Timmers

Multiple endocrine neoplasia type 1 (MEN1) is heriditary syndrome characterised by the occurrence of parathyroid, gastroenteropancreatic and pituitary tumours. The gene product, menin, co-activates gene transcription by recruiting histone methyltransferases for lysine 4 of histone H3 (H3K4). We investigated whether in MEN1 tumours global changes in H3K4 trimethylation (H3K4me3) occur or whether alterations in gene expression can be observed. By immunohistochemistry we found that global levels of H3K4me3 are not affected in MEN1-related parathyroid adenomas. Menin can interact directly with the vitamin D receptor (VDR) and enhance the transcriptional activity of VDR. Messenger RNA levels of VDR target genes and were significantly lower in MEN1 parathyroid adenomas compared to normal tissue. Thus, aberrant gene expression in MEN1 tumours is not caused by lower global H3K4me3, but rather by specific effects on genes that are regulated by menin-interacting proteins, such as VDR.

Mots clés: Multiple endocrine neoplasia type 1; Menin; Parathyroid adenoma; Vitamin D receptor; Histone methyltransferase; Gene transcription; Histone modification

Koen M.A. Dreijerink, Radhika A. Varier, Rick van Nuland, Roel Broekhuizen, Gerlof D. Valk, et al.. Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas. Molecular and Cellular Endocrinology, 2009, 313 (1-2), pp.1. ⟨10.1016/j.mce.2009.08.020⟩. ⟨hal-00522862⟩