%0 Journal Article %T The Drosophila methyl-DNA binding protein MBD2/3 interacts with the NuRD complex via p55 and MI-2 %A Joachim Marhold %A Alexander Brehm %A Katja Kramer %J BMC Molecular Biology %D 2004 %I BioMed Central %R 10.1186/1471-2199-5-20 %X The two MBD2/3 isoforms precisely cofractionated with NuRD proteins during gel filtration of extracts derived from early and late embryos. In addition, we demonstrate that MBD2/3 forms multimers, and engages in specific interactions with the p55 and MI-2 subunits of the Drosophila NuRD complex.Our data provide novel insights into the association between Drosophila MBD2/3 and NuRD proteins. Additionally, this work provides a first analysis of the architecture of the Drosophila NuRD complex.Methyl-DNA binding proteins are connecting DNA methylation to transcriptional silencing [1-4]. Up to now, six methyl-DNA binding proteins could be identified in vertebrates [5]. MeCP2, MBD2 and MBD3 can be found in large chromatin complexes containing histone deacetylase activity [1,6,4,3] whereas MBD4 is involved in DNA mismatch-repair [7]. MBD1 has been shown to repress transcription in cell culture [8] and recruits the histone H3-K9 methyltransferase SETDB1 to the chromatin assembly factor CAF-1 during S phase [9]. MBD2, which can bind methylated DNA [6], is a transcriptional repressor recruiting a Nucleosome Remodelling and Deacetylase complex (NuRD) to methylated CpG dinucleotides [6,3], whereas mammalian MBD3, which is not able to bind methylated DNA [10] is an integral component of NuRD [3]. Kaiso, a transcriptional repressor protein, can bind directly to CpG methylated DNA even though it lacks a conserved methyl-DNA binding domain [11]. Kaiso is a component of a subpopulation of MeCP1 complexes that lack MBD2 [11].The Drosophila gene MBD2/3 encodes a protein, which shares high homology to mammalian MBD2 and MBD3 [12,4]. Due to differential splicing, Drosophila MBD2/3 is expressed in two isoforms, the smaller one is lacking part of the putative methyl-DNA binding domain [12-15]. The large isoform is expressed during early development, whereas the small isoform can only be detected during late embryogenesis [14,15]. In insect cells expressing only the small MBD2/3 isoform, th %U http://www.biomedcentral.com/1471-2199/5/20