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

Buqing Ye, Benyu Liu, Liuliu Yang, Guanling Huang, Lu Hao, Pengyan Xia, Shuo Wang, Ying Du, Xiwen Qin, Pingping Zhu, Jiayi Wu, Nobuo Sakaguchi, Junyan Zhang and Zusen Fan ()
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Buqing Ye: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Benyu Liu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Liuliu Yang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Guanling Huang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Lu Hao: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Pengyan Xia: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Shuo Wang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Ying Du: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Xiwen Qin: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Pingping Zhu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Jiayi Wu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Nobuo Sakaguchi: Osaka University
Junyan Zhang: Harvard Medical School
Zusen Fan: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01788-7

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