The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression

Yong Jin Yang, Jeung Whan Han, Hong-Duk Youn, Eun Jung Cho

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)

Abstract

Parafibromin, a component of the RNA polymerase II-associated PAF1 complex, is a tumor suppressor linked to hyperparathyroidism-jaw tumor syndrome and sporadic parathyroid carcinoma. Parafibromin induces cell cycle arrest by repressing cyclin D1 via an unknown mechanism. Here, we show that parafibromin interacts with the histone methyltransferase, SUV39H1, and functions as a transcriptional repressor. The central region (128-227 amino acids) of parafibromin is important for both the interaction with SUV39H1 and transcriptional repression. Parafibromin associated with the promoter and coding regions of cyclin D1 and was required for the recruitment of SUV39H1 and the induction of H3 K9 methylation but not H3 K4 methylation. RNA interference analysis showed that SUV39H1 was critical for cyclin D1 repression. These data suggest that parafibromin plays an unexpected role as a repressor in addition to its widely known activity associated with transcriptional activation. Parafibromin as a part of the PAF1 complex might downregulate cyclin D1 expression by integrating repressive H3 K9 methylation during transcription.

Original languageEnglish
Article numbergkp991
Pages (from-to)382-390
Number of pages9
JournalNucleic Acids Research
Volume38
Issue number2
DOIs
StatePublished - 10 Nov 2009

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Cyclin D1
Histones
Methylation
Neoplasms
Parathyroid Neoplasms
RNA Polymerase II
RNA Interference
Cell Cycle Checkpoints
Genetic Promoter Regions
Transcriptional Activation
Down-Regulation
Amino Acids

Cite this

Yang, Yong Jin ; Han, Jeung Whan ; Youn, Hong-Duk ; Cho, Eun Jung. / The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression. In: Nucleic Acids Research. 2009 ; Vol. 38, No. 2. pp. 382-390.
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The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression. / Yang, Yong Jin; Han, Jeung Whan; Youn, Hong-Duk; Cho, Eun Jung.

In: Nucleic Acids Research, Vol. 38, No. 2, gkp991, 10.11.2009, p. 382-390.

Research output: Contribution to journalArticleResearchpeer-review

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