The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin
Open accessAbstract
BACKGROUND Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are characteristic hallmarks of mammalian heterochromatin. H3-K9 methylation was recently shown to be a prerequisite for DNA methylation in Neurospora crassa and Arabidopsis thaliana. Currently, it is unknown whether a similar dependence exists in mammalian organisms. RESULTS Here, we demonstrate a physical and functional link between the Suv39h-HP1 histone methylation system and DNA methyltransferase 3b (Dnmt3b) in mammals. Whereas in wild-type cells Dnmt3b interacts with HP1 alpha and is concentrated at heterochromatic foci, it fails to localize to these regions in Suv39h double null (dn) mouse embryonic stem (ES) cells. Consistently, the Suv39h dn ES cells display an altered DNA methylation profile at pericentric satellite repeats, but not at other repeat sequences. In contrast, H3-K9 trimethylation at pericentric heterochromatin is not impaired in Dnmt1 single- or Dnmt3a/Dnmt3b double-deficient ES cells. We also show that pericentric heterochromatin is not transcriptionally inert and can give rise to transcripts spanning the major satellite repeats. CONCLUSIONS These data demonstrate an evolutionarily conserved pathway between histone H3-K9 methylation and DNA methylation in mammals. While the Suv39h HMTases are required to direct H3-K9 trimethylation and Dnmt3b-dependent DNA methylation at pericentric repeats, DNA methylation at centromeric repeats occurs independent of Suv39h function. Thus, our data also indicate a more complex interrelatedness between histone and DNA methylation systems in mammals. Both methylation systems are likely to be important in reinforcing the stability of heterochromatic subdomains and thereby in protecting genome integrity.
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DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143
Self-citationTargeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984
Self-citationMethylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., & Jenuwein, T. (2001) · Nature · doi:10.1038/35065132 · Cited by 2,868
Self-citationLewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90610-o · Cited by 1,371
De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells
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Cited by
Epigenetics in human disease and prospects for epigenetic therapy
Egger, G., Liang, G., Aparicio, A., & Jones, P. A. (2004) · Nature · doi:10.1038/nature02625 · Cited by 3,232
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
DNA methylation and human disease
Robertson, K. D. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1655 · Cited by 2,864
Sharma, S., Kelly, T. K., & Jones, P. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp220 · Cited by 2,637
Genomic DNA methylation: the mark and its mediators.
Klose, R. J., & Bird, A. P. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.008 · Cited by 2,501
Metadata
- Authors
- Lehnertz, B., Ueda, Y., Derijck, A. A. H. A., Braunschweig, U., Perez-Burgos, L., Kubicek, S., Chen, T., Li, E., Jenuwein, T., & Peters, A. H. F. M.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 13
- Issue
- 14
- Pages
- 1192-1200
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1991667131
- Cited by
- 1,245
- References
- 6
- FWCI
- 23.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lehnertz, B., Ueda, Y., Derijck, A. A. H. A., Braunschweig, U., Perez-Burgos, L., Kubicek, S., Chen, T., Li, E., Jenuwein, T., & Peters, A. H. F. M. (2003). Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin. Current Biology. https://doi.org/10.1016/s0960-9822(03)00432-9
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