Identifying Tissue Specific Distal Regulatory Sequences in the Mouse Genome

Epigenetic modifications, transcription factor (TF) availability and chromatin conformation influence how a genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. In this report, enhancer identification is first carried out using an enhancer associated feature in mouse erythroid cells. Taking advantage of public domain ChIP-Seq data sets in mouse embryonic stem cells, an integrative model is then used to assess features in enhancer prediction, and subsequently locate enhancers. Significant associations with multiple TF bound loci, higher expression in the closest genes, and active enhancer marks support functionality and tissue-specificity of these enhancers. Motif enrichment analysis further determines known and novel TFs regulating the target cell type. Furthermore, the features identified can facilitate more accurate enhancer prediction in other cell types.MAS