Dataset Information

A methyltransferase required for proper timing of the vernalization response in Arabidopsis.

ABSTRACT: Prolonged exposure to winter cold enables flowering in many plant species through a process called vernalization. In Arabidopsis, vernalization results from the epigenetic silencing of the floral repressor flowering locus C (FLC) via a Polycomb Repressive Complex 2 (PRC2)-mediated increase in the density of the epigenetic silencing mark H3K27me3 at FLC chromatin. During cold exposure, a gene encoding a unique, cold-specific PRC2 component, vernalization insensitive 3 (VIN3), which is necessary for PRC2-mediated silencing of FLC, is induced. Here we show that set domain group 7 (SDG7) is required for proper timing of VIN3 induction and of the vernalization process. Loss of SDG7 results in a vernalization-hypersensitive phenotype, as well as more rapid cold-mediated up-regulation of VIN3. In the absence of cold, loss of SDG7 results in elevated levels of long noncoding RNAs, which are thought to participate in epigenetic repression of FLC. Furthermore, loss of SDG7 results in increased H3K27me3 deposition on FLC chromatin in the absence of cold exposure and enhanced H3K27me3 spreading during cold treatment. Thus, SDG7 is a negative regulator of vernalization, and loss of SDG7 creates a partially vernalized state without cold exposure.

SUBMITTER: Lee J

PROVIDER: S-EPMC4343098 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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A methyltransferase required for proper timing of the vernalization response in Arabidopsis.

Lee Joohyun J Yun Jae-Young JY Zhao Wei W Shen Wen-Hui WH Amasino Richard M RM

Proceedings of the National Academy of Sciences of the United States of America 20150120 7

Prolonged exposure to winter cold enables flowering in many plant species through a process called vernalization. In Arabidopsis, vernalization results from the epigenetic silencing of the floral repressor flowering locus C (FLC) via a Polycomb Repressive Complex 2 (PRC2)-mediated increase in the density of the epigenetic silencing mark H3K27me3 at FLC chromatin. During cold exposure, a gene encoding a unique, cold-specific PRC2 component, vernalization insensitive 3 (VIN3), which is necessary f ...[more]

PMID: 25605879

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Project description:BackgroundDisruptor of telomeric silencing 1-like (DOT1L) is a non-SET domain containing methyltransferase known to catalyze mono-, di-, and tri-methylation of histone 3 on lysine 79 (H3K79me). DOT1L-mediated H3K79me has been implicated in chromatin-associated functions including gene transcription, heterochromatin formation, and DNA repair. Recent studies have uncovered a role for DOT1L in the initiation and progression of leukemia and other solid tumors. The development and availability of small molecule inhibitors of DOT1L may provide new and unique therapeutic options for certain types or subgroups of cancer.MethodsIn this study, we examined the role of DOT1L in DNA double-strand break (DSB) response and repair by depleting DOT1L using siRNA or inhibiting its methyltransferase activity using small molecule inhibitors in colorectal cancer cells. Cells were treated with different agents to induce DNA damage in DOT1L-depleted or -inhibited cells and analyzed for DNA repair efficiency and survival. Further, rectal cancer patient samples were analyzed for H3K79me3 levels in order to determine whether it may serve as a potential marker for personalized therapy.ResultsOur results indicate that DOT1L is required for a proper DNA damage response following DNA double-strand breaks by regulating the phosphorylation of the variant histone H2AX (γH2AX) and repair via homologous recombination (HR). Importantly, we show that small molecule inhibitors of DOT1L combined with chemotherapeutic agents that are used to treat colorectal cancers show additive effects. Furthermore, examination of H3K79me3 levels in rectal cancer patients demonstrates that lower levels correlate with a poorer prognosis.ConclusionsIn this study, we conclude that DOT1L plays an important role in an early DNA damage response and repair of DNA double-strand breaks via the HR pathway. Moreover, DOT1L inhibition leads to increased sensitivity to chemotherapeutic agents and PARP inhibition, which further highlights its potential clinical utility. Our results further suggest that H3K79me3 can be useful as a predictive and or prognostic marker for rectal cancer patients.

Dataset Information

A methyltransferase required for proper timing of the vernalization response in Arabidopsis.

Publications

A methyltransferase required for proper timing of the vernalization response in Arabidopsis.

Similar Datasets

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