Dataset Information

A new role for histone demethylases in the maintenance of plant genome integrity.

ABSTRACT: Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development, and adaptation to environmental fluctuations of most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in Arabidopsis, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play distinct roles in H3K27me3 and H3K27me1 homeostasis. We show that failure to reset these chromatin marks during sexual reproduction results in the transgenerational inheritance of histone marks, which cause a loss of DNA methylation at heterochromatic loci and transposon activation. Thus, Jumonji-type histone demethylases play a dual role in plants by helping to maintain transcriptional states through development and safeguard genome integrity during sexual reproduction.

SUBMITTER: Antunez-Sanchez J

PROVIDER: S-EPMC7671693 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A new role for histone demethylases in the maintenance of plant genome integrity.

Antunez-Sanchez Javier J Naish Matthew M Ramirez-Prado Juan Sebastian JS Ohno Sho S Huang Ying Y Dawson Alexander A Opassathian Korawit K Manza-Mianza Deborah D Ariel Federico F Raynaud Cecile C Wibowo Anjar A Daron Josquin J Ueda Minako M Latrasse David D Slotkin R Keith RK Weigel Detlef D Benhamed Moussa M Gutierrez-Marcos Jose J

eLife 20201027

Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development, and adaptation to environmental fluctuations of most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in <i>Arabidopsis</i>, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play ...[more]

PMID: 33107825

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Project description:BACKGROUND:Epigenetic modifications, particularly DNA methylation and posttranslational histone modifications regulate heritable changes in transcription without changes in the DNA sequence. Despite a number of studies showing clear links between environmental factors and DNA methylation, little is known about the effect of environmental factors on the recently identified histone lysine methylation. Since their identification numerous studies have establish critical role played by these enzymes in mammalian development. OBJECTIVES:Identification of the Jumonji (Jmj) domain containing histone lysine demethylase have added a new dimension to epigenetic control of gene expression by dynamic regulation of histone methylation marks. The objective of our study was to evaluate the effect of prohexadione and trinexapac, widely used plant growth regulators of the acylcyclohexanediones class, on the enzymatic activity of histone lysine demethylases and histone modifications during the neural stem/progenitor cell differentiation. METHODS:Here we show that prohexadione, but not trinexapac, directly inhibits non-heme iron (II), 2-oxoglutarate-dependent histone lysine demethylase such as Jmjd2a. We used molecular modeling to show binding of prohexadione to Jmjd2a. We also performed in vitro demethylation assays to show the inhibitory effect of prohexadione on Jmjd2a. Further we tested this molecule in cell culture model of mouse hippocampal neural stem/progenitor cells to demonstrate its effect toward neuronal proliferation and differentiation. RESULTS:Molecular modeling studies suggest that prohexadione binds to the 2-oxoglutarate binding site of Jmjd2a demethylase. Treatment of primary neural stem/progenitor cells with prohexadione showed a concentration dependent reduction in their proliferation. Further, the prohexadione treated neurospheres were induced toward neurogenic lineage upon differentiation. CONCLUSIONS:Our results describe an important chemico-biological interaction of prohexadione, in light of critical roles played by histone lysine demethylases in human health and diseases.

Dataset Information

A new role for histone demethylases in the maintenance of plant genome integrity.

Publications

A new role for histone demethylases in the maintenance of plant genome integrity.

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