Genome-wide mapping of bivalent histone modifications in hepatic stem/progenitor cells

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The “bivalent domain,” a distinctive histone modification signature, is characterized by repressive trimethylation of histone H3 at lysine 27 (H3K27me3) and active trimethylation of histone H3 at lysine 4 (H3K4me3) marks. Maintenance and dynamic resolution of these histone marks play important roles in regulating differentiation processes in various stem cell systems. However, little is known regarding their roles in hepatic stem/progenitor cells. In the present study, we conducted the chromatin immunoprecipitation (ChIP) assay followed by high-throughput DNA sequencing (ChIP-seq) analyses in purified delta-like 1 protein (Dlk + ) hepatic stem/progenitor cells and successfully identified 562 genes exhibiting bivalent domains within 2 kb of the transcription start site. Gene ontology analysis revealed that these genes were enriched in developmental functions and differentiation processes. Microarray analyses indicated that many of these genes exhibited derepression after differentiation toward hepatocyte and cholangiocyte lineages. Among these, 72 genes, including Cdkn2a and Sox4, were significantly upregulated after differentiation toward hepatocyte or cholangiocyte lineages. Knockdown of Sox4 in Dlk + cells suppressed colony propagation and resulted in increased numbers of albumin + /cytokeratin 7 + progenitor cells in colonies. These findings implicate that derepression of Sox4 expression is required to induce normal differentiation processes. In conclusion, combined ChIP-seq and microarray analyses successfully identified bivalent genes. Functional analyses of these genes will help elucidate the epigenetic machinery underlying the terminal differentiation of hepatic stem/progenitor cells.

Detaljer

Författare
  • Kengo Kanayama
  • Tetsuhiro Chiba
  • Motohiko Oshima
  • Hiroaki Kanzaki
  • Shuhei Koide
  • Atsunori Saraya
  • Satoru Miyagi
  • Naoya Mimura
  • Yuko Kusakabe
  • Tomoko Saito
  • Sadahisa Ogasawara
  • Eiichiro Suzuki
  • Yoshihiko Ooka
  • Hitoshi Maruyama
  • Atsushi Iwama
  • Naoya Kato
Enheter & grupper
Externa organisationer
  • Chiba University Hospital
  • Chiba University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Utvecklingsbiologi
  • Cell- och molekylärbiologi
Originalspråkengelska
Artikelnummer9789240
TidskriftStem Cells International
Volym2019
StatusPublished - 2019
PublikationskategoriForskning
Peer review utfördJa