Suppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2

Nat Commun. 2017 Nov 15;8(1):1518. doi: 10.1038/s41467-017-01788-7.

Abstract

Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A.Z and transcription factor PU.1 to key lymphoid fate regulator genes. Furthermore, Znhit1 deletion also abrogates H2A/H2A.Z exchange in MPPs. Thus Pcid2 controls lymphoid lineage commitment through the regulation of SRCAP remodelling activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Cells, Cultured
  • Chromatin Assembly and Disassembly*
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism*
  • Mice, Knockout
  • Microscopy, Confocal
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*

Substances

  • Histones
  • Nuclear Proteins
  • PCID2 protein, human
  • Adenosine Triphosphatases
  • SRCAP protein, human