A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development
Anna Luiza Facchetti Vinhaes Assumpçãoa b, Guoping Fuc, Deependra Kumar Singha b, Zhanping Lua b, Ashley M. Kuehnla b, Rene Welchd e, Irene M. Onga d e, Renren Wenc, Xuan Pana b✉
- aCarbone Cancer Center, UW-Madison Blood Research Program, Madison, WI 53705, USA
- bDepartment of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 57306, USA
- cVersiti, Blood Research Institute, 8701 Watertown Plank Road, Milwaukee, WI 53223, USA
- dDepartment of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, 610 Walnut St, Madison, WI 53726, USA
- eDepartment of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, 750 Highland Ave, Madison, WI 53705, USA
- ✉Corresponding author
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Abstract
Yin Yang 1 (YY1) is a ubiquitous transcription factor and mammalian Polycomb Group protein (PcG) with important functions for regulating lymphocyte development and stem cell self-renewal. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that result in 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 the hematopoietic system results in an early T cell developmental blockage at the double negative (DN) 1 stage with reduced Notch1 signaling. There is a lineage-specific requirement for YY1 PcG function. YY1 PcG domain is required for T and B cell development but not necessary for myeloid cells. YY1 functions in early T cell development are multicomponent and involve both PcG-dependent and -independent regulations. Although YY1 promotes early T cell survival through its PcG function, its function to promote the DN1-to-DN2 transition and Notch1 expression and signaling is independent of its PcG function. Our results reveal how a ubiquitously expressed PcG protein mediates lineage-specific and context-specific functions to control early T cell development.
TL;DRIt is demonstrated that a conditional knockout of Yy1 in the hematopoietic system results in an early T cell developmental blockage at the double negative (DN) 1 stage with reduced Notch1 signaling. (Semantic Scholar)