GSE50111
Genome-wide Twist1 occupancy in endocardial cushion cells, embryonic limb buds, and peripheral nerve sheath tumor cells
The basic helix-loop-helix transcription factor Twist1 has a well-documented role in mesenchymal populations of the developing embryo, such as endocardial cushion (ECC) mesenchymal cells and limb buds, and during cancer development and progression.  Whether Twist1 regulates the same transcriptional targets in different cell types has yet to be investigated.  Through chromatin immunoprecipitation followed by sequencing (Chip-seq) analysis, the cell type-specific genome-wide occupancy of Twist1 was investigated in ECCs, limb buds and mouse peripheral nerve sheath tumor (PNST) cells.  Twist1 binds mainly in a cell type-specific manner, with very few common genomic regions occupied by Twist1 in different cell types.  Genes associated with binding peaks in each cell type are related to known Twist1 cellular functions in ECCs, limb buds, and cancer cells.  We found that cell type-specific binding of Twist1 may be influenced by histone modifications or co-factors.   Binding regions were located in several Wnt pathway associated genes, supporting a link between Twist1 and Wnt signalling in ECCs, limb buds, and PNST cells.  These data suggest that similar functions are regulated by Twist1 in ECCs, limb buds, and PNST cells in a cell type-specific manner, and provide insights into possible mechanisms utilized for cell type-specificity of Twist1 binding. Overall design: We compare Twist1 genome occupancy in mouse embryonic day (E) 12.5 endocardial cushion mesenchymal cells, E10.5 forelimb buds, and a mouse peripheral nerve sheath tumor cell line.