Analysis of Local Chromatin States Reveals Gene Transcriptional Potential during Mouse Neural Progenitor Cell Differentiation

Chromatin dynamics plays a critical role in cell fate determination and maintenance through regulating expression of genes essential for development and differentiation. In mouse embryonic stem cells (mESCs) the maintenance of pluripotency coincides with a poised chromatin state containing both active and repressive histone modifications. However, structural feature of poised chromatin is largely uncharacterized. By adopting a mild time-course MNase-seq with computational analysis, we found that low-compact chromatin in mESCs features two groups, one in more open regions, corresponding to an active state, the other enriched with bivalent histone modifications, considered as the poised state. We further devised a parameter named Expression Potential Index (EPI) to quantify the transcription potential based on the dynamic changes of MNase-seq signals at promoter regions. The use of EPI provided effectively prediction of gene activation potential, and more importantly revealed a few novel developmental factors essential for mouse neural progenitor cells (NPCs) differentiation. We herein present a delineation of distinct populations of low-compacted chromatin which correspond to epigenetically active and bivalent regions in mESCs, and provide an efficient tool to effectively predict gene transcriptional potential via quantitatively analyzing local chromatin states during development and differentiation.