title: PIAS1 SUMO ligase regulates the self-renewal and differentiation of hematopoietic stem cells.
abstract: The selective and temporal DNA methylation plays an important role in the self-renewal and differentiation of hematopoietic stem cells (HSCs), but the molecular mechanism that controls the dynamics of DNA methylation is not understood. Here, we report that the PIAS1 epigenetic pathway plays an important role in regulating HSC self-renewal and differentiation. PIAS1 is required for maintaining the quiescence of dormant HSCs and the long-term repopulating capacity of HSC. Pias1 disruption caused the abnormal expression of lineage-associated genes. Bisulfite sequencing analysis revealed the premature promoter demethylation of Gata1, a key myeloerythroid transcription factor and a PIAS1-target gene, in Pias1(-/-) HSCs. As a result, Pias1 disruption caused the inappropriate induction of Gata1 in HSCs and common lymphoid progenitors (CLPs). The expression of other myeloerythroid genes was also enhanced in CLPs and lineage-negative progenitors, with a concurrent repression of B cell-specific genes. Consistently, Pias1 disruption caused enhanced myeloerythroid, but reduced B lymphoid lineage differentiation. These results identify a novel role of PIAS1 in maintaining the quiescence of dormant HSCs and in the epigenetic repression of the myeloerythroid program.
authors.affiliation: Division of Hematology-Oncology Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Yee
authors.forename: Samuel
authors.initials: S
authors.lastname: Tahk
authors.forename: Ryan
authors.initials: R
authors.lastname: Mackie
authors.forename: Cary
authors.initials: C
authors.lastname: Hsu
authors.forename: Ke
authors.initials: K
authors.lastname: Shuai
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D060833:Cellular Microenvironment / Q000235:genetics; D044127:Epigenesis, Genetic; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050828:Protein Inhibitors of Activated STAT / Q000502:physiology*; D055153:Stem Cell Niche / Q000235:genetics
chemical_list: C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT