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

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

Ye B1, Liu B1,2, Yang L1,2, Huang G1,2, Hao L1,2, Xia P1, Wang S1, Du Y1, Qin X1,2, Zhu P1, Wu J1,2, Sakaguchi N3, Zhang J4, Fan Z5,6.

Author information

1
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2
University of Chinese Academy of Sciences, Beijing, 100049, China.
3
WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
4
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA.
5
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. fanz@moon.ibp.ac.cn.
6
University of Chinese Academy of Sciences, Beijing, 100049, China. fanz@moon.ibp.ac.cn.

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.

PMID:
29138493
PMCID:
PMC5686073
DOI:
10.1038/s41467-017-01788-7
[Indexed for MEDLINE]
Free PMC Article

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