UC Irvine

After fertilization, the unified genome from the egg and sperm must go through reprogramming to reset the newly formed zygotic genome for the onset of the embryonic development. Maternally-deposited transcriptions factors (TFs) initiate this process that includes modification of the inherited epigenetic landscape. The subsequent differential expression of zygotic genes drives the formation of distinctive cell types - ectoderm, mesoderm, and endoderm - known as germ layer specification. However, the regulation of maternal TFs with epigenetic remodeling during germ layer specification is not well known.

To investigate the role of TFs and its relationship with chromatin during early embryogenesis, I have optimized Deoxyribonuclease I (DNase I) hypersensitive sites sequencing (DNase-seq) in early Xenopus embryos. DNase-seq identifies the genome-wide open chromatin regions that are accessible to regulatory factors.

I also used Foxh1-deficient Xenopus embryos to study its function in chromatin remodeling. I found that Foxh1 is required for the recruitment of a core subunit of polycomb repressive complex 2 (PRC2), Ezh2, and the regional activity of H3K27me3. Differential enrichment of H3K27me3 between ectodermal and endodermal germ layers of the Xenopus embryos suggests that Foxh1 directs Ezh2 recruitment to regulate histone modification both temporally and spatially. Ezh2 binding is also associated with another maternal TF, Sox3, which suggests that the combinatorial bindings of multiple maternal TFs fine-tune the temporal and spatial gene expression to induce the correct cell types in an embryo.

My findings provide a more comprehensive understanding of how maternal TFs regulate the epigenetic landscape during early vertebrate embryogenesis. I propose a model where Foxh1 recruits Ezh2 to mark epigenetically the regulatory regions of germ layer-specific genes to promote and maintain embryonic germ layer specification.