Suppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2, Nat Commun, 8(1):1518,15 Nov 2017

Nature Communications, Vol 8, Issue 1, Artical No. 1518,15 Nov 2017，DOI: 10.1038/s41467-017-01788-7

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, Zusen Fan

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. Haematopoiesis and the generation of lymphoid cell subsets are controlled by delicate genetic programs enforced via epigenetic regulation. Here the authors show that Pcid2 interacts with ZNHIT1, a component of the SRCAP chromatin remodelling complex, to critically modulate the differentiation of multipotent progenitors.

文章链接：http://www.nature.com/articles/s41467-017-01788-7