Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

Figure 2

Changes in epigenetic signatures upon HSC differentiation and lineage commitment. Multipotency genes are actively transcribed in hematopoietic stem cells (HSC) to maintain stemness and self-renewal. Promoter and enhancer regions are labelled with activating H3K4 methylation marks (green hexagons) and unmethylated CpG islands (white circles). Key genes, important for lineage commitment and differentiation into progenitor cells of the myeloid (common myeloid progenitors (CMP)) or lymphoid lineage (common lymphoid progenitors (CLP)), are kept in a paused state mainly by the counteracting histone methylation marks H3K27me3 (repressive) and H3K4me3 (activating) in gene regulatory regions, termed as bivalent signatures (yellow hexagons). Upon lineage commitment, multipotency genes are silenced by repressive histone methylation marks (e.g., H3K27m3, H3K9me3, and red hexagons) and partially by gene-specific de novo methylation of CpG islands (grey circles). Upon differentiation bivalent chromatin signatures are resolved depending on lineage choice: paused genes become either activated transcriptionally by accumulation of activating H3K4me3 marks and loss of repressive H3K27me3 or silenced by loss of H3K4me3 and accumulation of H3K27me3 and partially by gene-specific methylation of CpG islands.