Dynamic promoter-enhancer contacts contribute to spatiotemporal gene expression during mouse fetal development

While a rich set of putative cis-regulatory sequences involved in mouse fetal development has been annotated recently based on chromatin accessibility and histone modification patterns, delineating their roles in developmentally regulated gene expression continues to be challenging due to a lack of information regarding their putative target genes. To fill this gap, we examined the tissue-to-tissue variability and developmental dynamics of chromatin contacts between gene promoters and distal sequences genome-wide in mouse embryos. Among the 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes, many occur between promoters and putative enhancers located hundreds of kilobases away. More than 75% of the chromatin interactions coincide with the binding of CTCF at one or both anchors, underscoring a broad role for this chromatin organizer in developmentally regulated 3D chromatin conformation. The predicted target genes of 15,098 candidate enhancers demonstrate highly tissue-specific and developmental stage restricted expression patterns, and may facilitate the annotation of noncoding risk variants associated with human diseases.