Characterization of Histone Modifications on Lineage-Affiliated Genes During Hematopoietic Stem Cell Differentiation

Abstract 4784

Hematopoietic stem cells (HSCs) are multipotent stem cells capable of self-renewal and multi-lineage differentiation. Though it has been shown that multiple factors take part in the maintenance of HSCs’ multipotency and differentiation potential, the mechanisms are unclear. Recent studies showed that histone modifications play an important role in maintenance of embryonic stem cells pluripotency and differentiation. To characterize the histone modification patterns of different lineages, HSCs were collected from umbilical cord blood and induced to differentiate to granulocytic, erythroid, and megakarytic in vitro. genes during HSC differentiation. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) technology was adopted to investigate the dynamic changes of histone modifications on lineage specific transcription factors and lineage–affiliated genes. Our results showed a certain level of H4 acetylation and H3 acetylation together with high level of H3K4me2 and low level of H3K4me3, H3K9me3 and H3K27me3 were present in lineage specific genes in CD34⁺CD38^- HSCs. As CD34⁺CD38^- cells differentiated, the modification level of acH3, acH4, H3K4me2, H3K9me3 and H3K27me3 on lineage specific genes remained the same, while H3K4me3 level increased greatly. In non-lineage specific genes, the acH3 and acH4 levels decreased, and H3K4me3 level remain at low level, while H3K9me3 and H3K27me3 levels increased. Thus, our data suggested that histone modifications played an important role in maintenaning the multipotency and differentiation capability of hematopoietic stem cells.