Transcriptional repression by Drosophila methyl-CpG-binding proteins

K. Roder, M. S. Hung, T. L. Lee, T. Y. Lin, H. Xiao, K. I. Isobe, J. L. Juang, C. K.J. Shen

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Abstract

C methylation at genomic CpG dinucleotides has been implicated in the regulation of a number of genetic activities during vertebrate cell differentiation and embryo development. The methylated CpG could induce chromatin condensation through the recruitment of histone deacetylase (HDAC)-containing complexes by methyl-CpG-binding proteins. These proteins consist of the methylated-DNA binding domain (MBD). Unexpectedly, however, several studies have identified MBD-containing proteins encoded by genes of Drosophila melanogaster, an invertebrate species supposed to be void of detectable m5CpG. We now report the genomic structure of a Drosophila gene, dMBD2/3, that codes for two MBD-containing, alternatively spliced, and developmentally regulated isoforms of proteins, dMBD2/3 and dMBD2/3Δ. Interestingly, in vitro binding experiments showed that as was the case for vertebrate MBD proteins, dMBD2/3Δ could preferentially recognize m5CpG-containing DNA through its MBD. Furthermore, dMBD2/3Δ as well as one of its orthologs in mouse, MBD2b, could function in human cells as a transcriptional corepressor or repressor. The activities of HDACs appeared to be dispensable for transcriptional repression by dMBD2/3Δ. Finally, dMBD2/3Δ also could repress transcription effectively in transfected Drosophila cells. The surprisingly similar structures and characteristics of the MBD proteins as well as DNA cytosine (C-5) methyltransferase-related proteins in Drosophila and vertebrates suggest interesting scenarios for their roles in eukaryotic cellular functions.

Original languageEnglish
Pages (from-to)7401-7409
Number of pages9
JournalMolecular and Cellular Biology
Volume20
Issue number19
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Roder, K., Hung, M. S., Lee, T. L., Lin, T. Y., Xiao, H., Isobe, K. I., Juang, J. L., & Shen, C. K. J. (2000). Transcriptional repression by Drosophila methyl-CpG-binding proteins. Molecular and Cellular Biology, 20(19), 7401-7409. https://doi.org/10.1128/MCB.20.19.7401-7409.2000