A Drosophila MBD family member is a transcriptional corepressor associated with specific genes

Abstract

DNA methylation in Drosophila melanogaster is restricted temporally during development and occurs at a significantly lower frequency than in mammals. Thus, the regulatory functions, if any, of this form of DNA modification in Drosophila are unclear. However, the presence of homologs of vertebrate methyl-CpG-binding proteins implies functional consequences for DNA methylation in flies. This work describes the properties of dMBD-like, a Drosophila homolog of vertebrate MBD2 and MBD3. dMBD-like and dMBD-likeDelta (a splice variant) failed to bind model methylated DNA probes, inconsistent with their function as mediators of methyl CpG-directed transcriptional repression. However, the MBD-like proteins exhibit transcriptional and biochemical properties consistent with roles as components of a histone deacetylase-dependent corepressor complex similar to the vertebrate Mi-2 complex. The two proteins are differentially expressed during development, suggesting functional specialization. dMBD-like and/or dMBD-likeDelta is present at the chromocenter on larval polytene chromosomes as well as at discrete bands interspersed along the euchromatic chromosome arms, many of which are coincident with known ecdysone-induced loci. This banding pattern suggests gene-specific regulatory functions for dMBD-like and the Drosophila Mi-2 complex.