Suppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29138493.
- Also identified by DOI 10.1038/s41467-017-01788-7 and PMC identifier 5686073.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adenosine Triphosphatases
- Cell Differentiation
- Chromatin Assembly and Disassembly
- Lymphoid Progenitor Cells
- Multipotent Stem Cells
- Nuclear Proteins