Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin

Lehnertz, Bernhard; Ueda, Yoshihide; Derijck, Alwin A.H.A.; Braunschweig, Ulrich; Perez-Burgos, Laura; Kubicek, Stefan; Chen, Taiping; Li, En; Jenuwein, Thomas; Peters, Antoine H.F.M.

doi:10.1016/s0960-9822(03)00432-9

Cited by 1,121 publications

(1,018 citation statements)

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“…The same result was obtained in A. thaliana by mutations of Kryptonite gene, a relative of Su(var)H3-K9 methyltransferase, in this case the CpNpG methylated sequences were largely demethylated while methylation status of CpGs remained unchanged [73]. In mice, mutation of the two Su(var)3-9 homologs has a relatively minor effect on cytosine methylation and causes partial demethylation of major satellite regions of pericentromeric heterochromatin [74]. These data suggest a clear dependence of DNA methylation on histone H3 methylation.…”

Section: The Connection Between Dna Met Hy-lation and Other Epigenetisupporting

confidence: 69%

Dynamic and reversibility of heterochromatic gene silencing in human disease

et al. 2005

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In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression, determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contribution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

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Section: The Connection Between Dna Met Hy-lation and Other Epigenetisupporting

confidence: 69%

Dynamic and reversibility of heterochromatic gene silencing in human disease

et al. 2005

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“…Wild-type and SUV39DN MEFs and ES cells were on a mixed genetic background of 129/SV and C57BL/6J origin 7,25 . We prepared MEFs from wildtype and SUV39DN embryos at embryonic day 12.5 as described 26 .…”

Section: Cellsmentioning

confidence: 99%

Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases

et al. 2003

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Telomeres are capping structures at the ends of eukaryotic chromosomes composed of TTAGGG repeats bound to an array of specialized proteins 1-3 . Telomeres are heterochromatic regions. Yeast and flies with defects in activities that modify the state of chromatin also have abnormal telomere function 4-6 , but the putative role of chromatin-modifying activities in regulating telomeres in mammals is unknown. Here we report on telomere length and function in mice null with respect to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called SUV39DN mice). Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3-Lys9) in heterochromatic regions 7 . We show that primary cells derived from SUV39DN mice have abnormally long telomeres relative to wild-type controls. Using chromatin immunoprecipitation (ChIP) analysis, we found that telomeres were enriched in diand trimethylated H3-Lys9 but that telomeres of SUV39DN cells had less dimethylated and trimethylated H3-Lys9 but more monomethylated H3-Lys9. Concomitant with the decrease in H3-Lys9 methylation, telomeres in SUV39DN cells had reduced binding of the chromobox proteins Cbx1, Cbx3 and Cbx5, homologs of Drosophila melanogaster heterochromatin protein 1 (HP1). These findings indicate substantial changes in the state of telomeric heterochromatin in SUV39DN cells, which are associated with abnormal telomere elongation. Taken together, the results indicate epigenetic regulation of telomere length in mammals by Suv39h1 and Suv39h2.The N-terminal tails of histones are subjected to post-translational modifications, including acetylation, methylation and phosphorylation, generating an extensive repertoire of chromatin structures 8,9 . Binding of factors that specifically recognize these modified histones mediate cellular responses 8,9 . Heterochromatic regions are enriched in methylated H3-Lys9, which creates a binding site for the chromobox proteins 9 , mediators of heterochromatin formation and epigenetic gene regulation. In D. melanogaster, HP1 is also required for telomere capping 4,5 . To investigate the impact of H3-Lys9 methylation on telomere length regulation and telomere function, we studied embryonic stem (ES) cells and mouse embryonic fibroblasts (MEFs) from SUV39DN mice 7 , which have less methylation of H3-Lys9 at the pericentric heterochromatin compared to wildtype mice 7 . First, we used terminal restriction fragment (TRF) analysis to estimate telomere length in these cells. Two independent SUV39DN ES cell cultures showed abnormally long telomeres, which were not present in wild-type ES cells (Fig. 1a). This finding was confirmed using MEFs (passage 1-2) derived from SUV39DN and wild-type littermate embryos (Fig. 1a). TRF analysis of increasing passages of the SUV39DN MEFs (D43) showed that the long telomeres in these MEFs were stable (Fig. 1b).Next, we carried out quantitative fluorescence in situ hybridization (Q-FISH) using a telomere-specific peptide nucleic acid probe. We determined the average telomere length for each ES-cell and ME...

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“…has been observed in diverse biological systems (Tamaru and Selker, 2001;Fahrner et al, 2002;Jackson et al, 2002;Fuks et al, 2003;Lehnertz et al, 2003;Tariq et al, 2003;Freitag et al, 2004). Therefore, the different H3-m 3 K9 states in the two species prompted us to investigate DNA methylation states in sperm-derived chromatins.…”

Section: Appearance Of H3-k9 Methylation In Pig But Not In Mouse Spmentioning

confidence: 99%

Gradual development of a genome‐wide H3‐K9 trimethylation pattern in paternally derived pig pronucleus

Jeong

Yeo

Park

et al. 2007

Developmental Dynamics

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The cytoplasm of a mature oocyte contains many protein complexes that are programmed to restructure incoming sperm chromatins on fertilization. Of the complicated biochemical events that these functional machineries control, the most impressive and important is epigenetic reprogramming. Despite its importance in epigenetic resetting, or "de-differentiation," of gamete genomes back to an incipient status, the mechanisms of epigenetic reprogramming do not seem to be conserved among mammals. Here, we report that, unlike in the mouse, the pig sperm-derived pronucleus is markedly trimethylated at lysine 9 of histone H3 (H3-m 3 K9), which might be associated with preservation of paternally derived cytosine methylation in pig zygotes. The male H3-m 3 K9 pattern is gradually established during pronucleus development, and this process occurs independently of DNA replication. Considering these unique epigenetic features, the pig zygote is, we believe, suited to serve as another model of epigenetic reprogramming that is antithetical to the well-characterized mouse model. Developmental Dynamics 236:1509 -1516, 2007.

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Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin

Cited by 1,121 publications

References 38 publications

Dynamic and reversibility of heterochromatic gene silencing in human disease

Dynamic and reversibility of heterochromatic gene silencing in human disease

Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases

Gradual development of a genome‐wide H3‐K9 trimethylation pattern in paternally derived pig pronucleus

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