ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing

Jacob, Yannick; Feng, Suhua; LeBlanc, Chantal; Bernatavichute, Yana V.; Stroud, Hume; Cokus, Shawn J.; Johnson, Lianna M.; Pellegrini, Matteo; Jacobsen, Steven E.; Michaels, Scott D.

doi:10.1038/nsmb.1611

Cited by 280 publications

(336 citation statements)

References 56 publications

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“…These findings suggest that histone methylation may play broad and important roles in regulating transcription. Consistent with this notion, several Arabidopsis histone methyltransferase (HMTase) mutants have been found to exhibit a myriad of developmental abnormalities (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Furthermore, transcriptome profiling studies have identified numerous genes that are misregulated in HMTase mutants (19,27,28).…”

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confidence: 61%

“…Specifically, class I SDGs are involved in H3K27me2/3, class II in H3K36me2/3, class III in H3K4me2/3, and class V in H3K9me2 (13,19,33,34). Class IV seems to be an exception: the Arabidopsis proteins SDG15 and SDG34 are responsible for H3K27me1 (24), but it is not clear whether the two yeast homologs (SET3 and SET4) possess HMTase activity. The HMTases responsible for H3K4me1, H3K9me1/3, and H3K36me1 have yet to be determined but are likely to be uncharacterized members in these five classes.…”

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confidence: 99%

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SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis

Guo

Law

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

143

162

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Posttranslational modifications of histones play important roles in modulating chromatin structure and regulating gene expression. We have previously shown that more than two thirds of Arabidopsis genes contain histone H3 methylation at lysine 4 (H3K4me) and that trimethylation of H3K4 (H3K4me3) is preferentially located at actively transcribed genes. In addition, several Arabidopsis mutants with locus-specific loss of H3K4me have been found to display various developmental abnormalities. These findings suggest that H3K4me3 may play important roles in maintaining the normal expression of a large number of genes. However, the major enzyme(s) responsible for H3K4me3 has yet to be identified in plants, making it difficult to address questions regarding the mechanisms and functions of H3K4me3. Here we described the characterization of SET DOMAIN GROUP 2 (SDG2), a large Arabidopsis protein containing a histone lysine methyltransferase domain. We found that SDG2 homologs are highly conserved in plants and that the Arabidopsis SDG2 gene is broadly expressed during development. In addition, the loss of SDG2 leads to severe and pleiotropic phenotypes, as well as the misregulation of a large number of genes. Consistent with our finding that SDG2 is a robust and specific H3K4 methyltransferase in vitro, the loss of SDG2 leads to a drastic decrease in H3K4me3 in vivo. Taken together, these results suggest that SDG2 is the major enzyme responsible for H3K4me3 in Arabidopsis and that SDG2-dependent H3K4m3 is critical for regulating gene expression and plant development.

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confidence: 61%

mentioning

confidence: 99%

SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis

Guo

Law

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

143

162

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“…Inactive promoters also harbor higher levels of methylation of lysine 9 on histone 3 (H3K9Me2) (36,37). Therefore, we performed ChIP on the Mcm2 promoter with an antibody against H3K9Me2 in P 4 E 2 and E 2 treated samples 3 h after treatment.…”

Section: Resultsmentioning

confidence: 99%

KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing

Ray

Pollard²

2012

Proc. Natl. Acad. Sci. U.S.A.

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In the epithelial compartment of the uterus, estradiol-17β (E 2 ) induces cell proliferation while progesterone (P 4 ) inhibits this response and causes differentiation of the cells. In this study, we identified the mechanism whereby E 2 and P 4 reciprocally regulate the expression of minichromosome maintenance (MCM)-2, a protein that is an essential component of the hexameric MCM-2 to 7 complex required for DNA synthesis initiation. We show in the uterine epithelium that Kruppel-like transcription (KLF) factors, KLF 4 and 15, are inversely expressed; most importantly, they bind to the Mcm2 promoter under the regulation of E 2 and P 4 E 2 , respectively. After P 4 E 2 exposure and in contrast to E 2 treated mice, the Mcm2 promoter displays increased histone 3 (H3) methylation and the recruitment of histone deacetylase 1 and 3 with the concomitant deacetylation of H3. This increased methylation and decreased acetylation is associated with an inhibition of RNA polymerase II binding, indicating an inactive Mcm2 promoter following P 4 E 2 treatment. Using transient transfection assays in the Ishikawa endometrial cell line, we demonstrate that Mcm2 promoter activity is hormonally stimulated by E 2 and that KLF15 inhibits this E 2 enhanced transcription. KLF15 expression also blocks Ishikawa cell proliferation through inhibition of MCM2 protein level. Importantly, in vivo expression of KLF15 in an estrogenized uterus mimics P 4 's action by inhibiting E 2 -induced uterine epithelial MCM-2 expression and DNA synthesis. KLF15 is therefore a downstream physiological mediator of progesterone's cell cycle inhibitory action in the uterine epithelium.endometrium | implantation | menstrual cycle | endometriosis E stradiol-17β (E 2 ) and progesterone (P 4 ) directs uterine preparation for pregnancy. These hormones synthesized cyclically in humans cause a sequential series of proliferative and differentiation events in the uterine stroma and epithelium that result in the epithelium being receptive to the blastocyst for attachment and subsequent implantation (1). Despite this close control of uterine cell proliferation, aberrant proliferative conditions of the human endometrium are common. For example, endometrial polyps and endometriosis are caused by inappropriate proliferation of the uterus, while unopposed estrogen stimulation is associated with menstrual irregularities and endometrial hyperplasia/adenocarcinoma (2). Endometrial cancer is the most common female genital tract malignancy and is responsible for 6% of cancer deaths of women in the United States and more worldwide (3). However, the molecular mechanisms underlying these pathologies are still obscure, as are the molecular mechanisms involved in normal hormonal regulation of cell proliferation in the endometrium, which is essential for successful pregnancy (4).The mouse uterus provides a unique in vivo model to study the regulation of epithelial cell proliferation as the physiological actions of E 2 and P 4 E 2 can be recapitulated in ovariectomized animals by treat...

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“…Recently, it was demonstrated that ATXR5 and ATXR6 proteins display H3K27 monomethyltransferase activity in vitro and in vivo and both are involved in heterochromatin formation and gene silencing (Jacob et al, 2009). They might also contribute to cell cycle regulation, perhaps at some stage during DNA replication, as they interact with the DNA polymerase processivity factor PCNA, and ATXR6 is a target of the E2F transcription factor (Raynaud et al, 2006).…”

Section: Histone Methylasesmentioning

confidence: 99%

Impact of nucleosome dynamics and histone modifications on cell proliferation during Arabidopsis development

et al. 2010

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Eukaryotic chromatin is a highly structured macromolecular complex of which DNA is wrapped around a histone-containing core. DNA can be methylated at specific C residues and each histone molecule can be covalently modified at a large variety of amino acids in both their tail and core domains. Furthermore, nucleosomes are not static entities and both their position and histone composition can also vary. As a consequence, chromatin behaves as a highly dynamic cellular component with a large combinatorial complexity beyond DNA sequence that conforms the epigenetic landscape. This has key consequences on various developmental processes such as root and flower development, gametophyte and embryo formation and response to the environment, among others. Recent evidence indicate that posttranslational modifications of histones also affect cell cycle progression and processes depending on a correct balance of proliferating cell populations, which in the context of a developing organisms includes cell cycle, stem cell dynamics and the exit from the cell cycle to endoreplication and cell differentiation. The impact of epigenetic modifications on these processes will be reviewed here.

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ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing

Cited by 280 publications

References 56 publications

SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis

SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis

KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing

Impact of nucleosome dynamics and histone modifications on cell proliferation during Arabidopsis development

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