The process whereby blood progenitor cells differentiate into red blood cells, known as erythropoiesis, is very similar between mice and humans. Yet, while studies of this process in mouse have substantially improved our knowledge of human erythropoiesis, recent work has shown a significant divergence in global gene expression across species, suggesting that extrapolation from mouse models to human is not always straightforward. In order to better understand these differences, we have performed a comparative epigenomic analysis of six histone modifications and four master transcription factors. By globally comparing chromatin structure across primary cells and model cell lines in both species, we discovered that while chromatin structure is well conserved at orthologous promoters, subtle changes are predictive of species-specific gene expression. Furthermore, we discovered that the genomic localizations of master transcription factors are poorly conserved, and species-specific losses or gains are associated with changes to the underlying chromatin structure and concomitant gene expression. By using our comparative epigenomics framework, we identified a putative human-specific cis-regulatory module that drives expression of human, but not mouse, GDF15, a gene implicated in iron homeostasis. Our results provide a resource to aid researchers in interpreting genetic and epigenetic differences between species.
Vyšlo v časopise: Altered Chromatin Occupancy of Master Regulators Underlies Evolutionary Divergence in the Transcriptional Landscape of Erythroid Differentiation. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004890 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004890
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