Methylation pattern

DAY J K, BAUER A M, DESBORDES C, ZHUANG Y, KIM B E, NEWTON L G, NEHRA V, FORSEE K M, MACDONALD R s, BESCH-wiLLiFORD c, HUANG T H and LUBAHN D B (2002) Genistein alters methylation patterns in mice. JNutr. 132 (8 Suppl) 2419S-23S. 

Sokol RZ Health Research Association, Inc., Los Angeles, CA Pb exposure in utero may induce an inherited change in DNA methylation patterns in Pb exposed pups, the mechanism by which Pb exposure during the critical time of sexual differentiation induces reproductive axis abnormalities in adulthood National Institute of Environmental Health Sciences... 

Saito A, Yamashita T, Mariko Y, Nosaka Y, Tsuchiya K, Ando T, Suzuki T, Tsurao T, Nakanishi O (1999) A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 96(8) 4592-4597 Schneider R, Bannister AJ, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T (2004) Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nature 6 73-77 Schwartz BE, Ahmad K (2005) Transcriptional activation triggers deposition and removal of the histone variant H3.3. Genes Dev 19 804-814... 

In contrast, lysine methylation seems to be an exceptionally stable modification. Early studies showed that turnover of histone methyl groups was even slower than turnover of the histones themselves (e.g., [26,27]). No conclusive evidence has yet been found for histone demethylating enzymes, and they may not exist [28]. It may be that removal of methylated histones mostly occurs passively, through post-replication chromatin assembly and replacement of old, methylated histones with new, unmethylated ones. However, the possibility remains that local methylation patterns may be more dynamic and may involve novel mechanisms for removal of methylated tails [28]. 

Noma, K., Allis, C.D., and Grewal, S.I.S. (2001) Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293, 1150-1155. 

Bird, A. (2002) DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21. 

DNA methylation patterns are heritably propagated in somatic lineage cells, but in some circumstances methylation of DNA is a dynamic process, especially during early embryogenesis. Remodeling of DNA methylation levels and patterns have been observed during development of many vertebrate species [5 9], the most dramatic example being the rapid demethylation of the mouse sperm DNA few... 

Fig. 1. Dynamics of DNA methylation levels during mouse development. The methylation patterns of the oocyte and the rapidly demethylated after fertilization sperm create the combined methylation patterns in the early mouse zygote. During the first two to three cleavage divisions, the 5mC levels decrease further and stay low through the blastula stage. Post-implantation, the mouse embryo genome is methylated de novo the CpG islands remain mostly unmethylated. The primordial germ cells remain unmethylated. During gametogenesis specific parental (maternal or paternal) patterns of DNA methylation are established at imprinted loci (for further details see Refs. [13, 14]) (re-drawn from Ref [4]).

Dnmtl Maintenance (functions after replication on hemimethylated DNA to restore existing methylation patterns in vitro can methylate non-methylated DNA) associates with histone deacetylase Adult/Embryo DNMTD die in utero DNA in these embryos is hypomethylated, imprinted genes are biallelically expressed ES cells from DNMTl mice are viable and capable of de novo methylation... 

Collectively, the results of these studies suggest a dominant role for DNA methylation, which dictates the acetylation status of the histones, and thereby, chromatin structure (Fig. 5c). The cells jealously preserve and inherit DNA methylation patterns, and respectively chromatin conformation, through mitosis. 

Yet another hypothesis considers the somatic variant Hle of histone HI, in its poly(ADP-ribosyl)ated isoform, as a nuclear traw -acting factor involved in maintaining the methylation pattern on DNA [161]. 

Thus, the poly(ADP-ribosyl)ation process is involved in determining and/or maintaining the methylation patterns on DNA. Considering the importance for cells to preserve these patterns, further research will be performed to find additional proof to convalidate one or another mechanism or to identify other possibilities. 

Gendrel, A.V., Lippman, Z., Yordan, C., Colot, V., and Martienssen, R.A. (2002) Dependence of heterochromatic histone H3 methylation patterns on the Arabidopsis gene DDMl. Science 297, 1871-1873. 

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