DamID for MBD3 in human breast cancer cell lines [Tiling Arrays]

Maintenance of chromatin structure is essential to eukaryotic life; dysregulation is known to be causal for aberrant development and disease. The Mi-2/nucleosome remodeling and histone deacetylase (NuRD) complex is a multiprotein machine proposed to regulate chromatin structure by nucleosome remodeling and histone deacetylation activities. We identified the localization of MBD3, a component of Mi-2/NuRD complex, in two breast cancer cell lines (MCF7 and MDA-MB-231) using ChIP-Seq. MBD3 showed cell-type specific localization with overlap across cell lines being less than 50%. MBD3 localized across gene bodies, peaking around the transcription start site (TSS). Contrary to existing models, MBD3 preferentially associated with CpG rich promoters marked by H3K4me3. These data suggest that MBD3, and by extension the Mi-2/NuRD complex, may have roles in fine tuning expression for active genes. These data represent an important first step in defining regulatory mechanisms by which Mi-2/NuRD complex controls chromatin structure and gene expression. DamID experiment was performed in human breast cancer cell lines (MCF-7 and MDA-MB-231) in triplicate. Samples were hybridized to NimbleGen Human Whole-Genome Tiling Arrays (0701_HG18_TILE_05_HX1 and 100718_HG18_TILE_05_HX1). MBD3-Dam material was hybridized over Dam-only control.