Polycomb Group Protein YY1 Is an Essential Regulator of Hematopoietic Stem Cell Quiescence
Zhanping Lu,
Courtney C. Hong,
Guangyao Kong,
Anna L.F.V. Assumpção,
Irene M. Ong,
Emery H. Bresnick,
Jing Zhang,
Xuan Pan
Affiliations
Zhanping Lu
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 57306, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Courtney C. Hong
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 57306, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Guangyao Kong
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave., Madison, WI 53705, USA; National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, PRC; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Anna L.F.V. Assumpção
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 57306, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Irene M. Ong
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave., Madison, WI 53705, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Emery H. Bresnick
Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave., Madison, WI 53705, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Jing Zhang
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave., Madison, WI 53705, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA
Xuan Pan
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 57306, USA; Carbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53706, USA; Corresponding author
Summary: Yin yang 1 (YY1) is a ubiquitous transcription factor and mammalian polycomb group protein (PcG) with important functions to regulate embryonic development, lineage differentiation, and cell proliferation. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that catalyze histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in hematopoietic stem cells (HSCs) decreases long-term repopulating activity and ectopic YY1 expression expands HSCs. Although the YY1 PcG domain is required for Igκ chain rearrangement in B cells, the YY1 mutant lacking the PcG domain retained the capacity to stimulate HSC self-renewal. YY1 deficiency deregulated the genetic network governing HSC cell proliferation and impaired stem cell factor/c-Kit signaling, disrupting mechanisms conferring HSC quiescence. These results reveal a mechanism for how a ubiquitously expressed transcriptional repressor mediates lineage-specific functions to control adult hematopoiesis.
