PUBLICATION

Smarca5 mediated epigenetic programming facilitates fetal HSPC development in vertebrates

Authors
Ding, Y., Wang, W., Ma, D., Liang, G., Kang, Z., Xue, Y., Zhang, Y., Wang, L., Heng, J., Zhang, Y., Liu, F.
ID
ZDB-PUB-200807-11
Date
2020
Source
Blood   137(2): 190-202 (Journal)
Registered Authors
Liu, Feng
Keywords
none
MeSH Terms
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • Chromosomal Proteins, Non-Histone/genetics
  • Chromosomal Proteins, Non-Histone/metabolism*
  • Epigenesis, Genetic/genetics*
  • Hematopoiesis/genetics*
  • Hematopoietic Stem Cells/cytology*
  • Mice
  • Mice, Inbred C57BL
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
32756943 Full text @ Blood
Abstract
Nascent HSPCs acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent- and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with Nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes