MFV3D Book Archive > Nonfiction 9 > Download DNA Methylation: Basic Mechanisms by W. Doerfler (auth.), Walter Doerfler, Petra Böhm (eds.) PDF

Download DNA Methylation: Basic Mechanisms by W. Doerfler (auth.), Walter Doerfler, Petra Böhm (eds.) PDF

By W. Doerfler (auth.), Walter Doerfler, Petra Böhm (eds.)

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46 48 49 50 55 56 59 60 References . . . . . . . . . . . . . . . . . . . . . . . . . 63 Abstract DNA methylation plays a pivotal role during development in mammals and is central to transcriptional silencing. The DNA methyltransferases (DNMTs) are responsible for the generation of genomic methylation patterns leading to gene silencing, but the underlying molecular basis remains largely shrouded in mystery.

The methyltransferase activity of each DNMT (present of not; de novo and/or maintenance) is described in the far right column 48 C. Brenner · F. 1 DNMT Structure A DNMT generally comprises two domains: a well-conserved catalytic domain in the carboxy-terminal part of the protein and a more variable regulatory domain in the amino-terminal region. Dnmt1 was the first enzyme to be isolated as a mammalian DNMT and the only one identified via a biochemical assay (Bestor et al. 1988; Yen et al. 1992). It has the largest amino-terminal domain of all known DNMTs.

3 Organization of the mouse MBD protein family. Numbers represent amino acid positions. coRID, corepressor interacting domain; CXXC, Cys-rich domain; (E)12 , Glu repeat; (GR)11 , Gly-Arg repeat; MBD, methyl-CpG-binding domain; HhH-GPD, DNA N-Glycosylase domain; TRD, transcriptional repressor domain MBD2 and 3 show a high conservation, sharing the same genomic structure except for their intron length (Hendrich et al. 1999a). Since homologous expressed sequence tags (ESTs) for MBD2/3 were also found in invertebrates, it is thought to represent the ancestral protein from which all other family members have been derived (Hendrich and Tweedie 2003).

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