Cell differentiation is a basic biology process. Epigenetic modifications, such as DNA methylation and posttranslational modifications of the various histone tails, are essential for normal development. Here, we analysis transcription factor binding dynamics during cell differentiation.
The human ES cells can differenatiate into early stages of endoderm (dEN), mesoderm (dME) and ectoderm (dEC). Directed differentiation of human ES cells into the three embryonic germ layers coupled with comprehensive TF binding analysis and integration with epigenomic data has allowed us to characterize differentiation-associated regulatory dynamics.
We carried out chromatin immunoprecipitation followed by sequencing (ChIP-seq) for core histone modifications (H3K4me1, H3K4me3, H3K27AcandH3K27me) as well as RNA sequencing (RNA-seq) of polyadenylated transcripts.
We find that targets of many lineage-specific factors associate with loss of DNA methylation in those germ layers, while factors that are expressed in more than one lineage (GATA4, GATA6, OTX2, SOX17) show a loss of DNA methylation at their targets in multiple cell types.
We also find a specific gain of DNA methylation for the targets of many TFs at later time points or in parallel time-points.
To summary, our work shows transcription factor binding, downstream signaling effectors, and the epigenome during human embryonic stem cell differentiation.