Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis

Abstract

Key Points Inactivation of Suz12 results in a rapid and marked exhaustion of the HSC pool. Lymphoid development is completely dependent on PRC2, but numerous myeloid lineages develop in the absence of PRC2.

Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis

“…Strikingly, a similar phenotype has been reported for Tie2-Cre Ezh2 fl/fl embryos, which also lacked definitive hematopoiesis and failed to develop beyond E13.5-E14.5, and in adult mice, Ezh2 was indispensable for lymphopoiesis (51)(52)(53). Similarly, deletion of Suz12 led to a rapid exhaustion of HSPCs and also impaired lymphopoiesis (54). Interestingly, Kdm2b, Ezh2, and Suz12 are all dispensable for myeloid differentiation.…”

Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics

“…17 Both oncogenic and tumor suppressor functions have been attributed to EZH2; it is likely that a delicately balanced gene dosage of the polycomb group proteins together with biologic context are crucial for stem cell homeostasis and determine oncogenic or tumor suppressor functions. 9,11 In contrast, EED and SUZ12 thus far appear to act predominantly as tumor suppressors; [7][8][9] however, additional studies are required to clarify the role of each polycomb group protein in different cellular contexts.…”

“…9,11 In malignant peripheral nerve sheath tumor, inactivation of PRC2 promotes cell proliferation and tumor growth. 6 PRC2 is composed of SUZ12, one EED isoform, and EZH1 or EZH2; this complex catalyzes the trimethylation of lysine 27 of histone H3, 12 a well-described mark of epigenetic silencing.…”

The roles of Polycomb group proteins in hematopoietic stem cells and hematological malignancies

“…Whereas 1 in 20,000 wild type E14.5 fetal liver HSCs exhibits long-term repopulating activity, only 1 in 400,000 Rae28 −/− HSCs does so. Transplantation of a Rae28 −/− fetal liver into a lethally irradiated mouse reduces the number of HSCs and cells of each lineage in bone marrow (BM), which indicates Suz12 Knockout Loss of maintenance of HSCs in fetal liver and BM, maturation arrest in T and B cell development [53] that Rae28 is important in the maintenance of HSC activity [39,40]. Fetal liver HSCs of mice deficient for Cbx2, a member of the CBX family, do not exhibit any obvious abnormalities and their number and repopulating ability are comparable to those of wild-type mice [31,41].…”

“…Loss of Suz12 causes HSCs to lose their ability to self-renew and exhausts the HSC pool. Additionally, although Suz12 is essential in lymphocyte formation, it is not necessary for differentiation of myeloid and megakaryocytic cells [53].…”