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Publication : Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1.

First Author  Nandakumar V Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  41 Pages  E3927-36
PubMed ID  24062447 Mgi Jnum  J:202315
Mgi Id  MGI:5518479 Doi  10.1073/pnas.1308888110
Citation  Nandakumar V, et al. (2013) Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1. Proc Natl Acad Sci U S A 110(41):E3927-36
abstractText  Histone modifications play critical roles in regulating immunity; however, little is known about the epigenetic control of natural killer (NK) cell development. Here, we found that NK cell development is severely impaired in mice deficient in the histone H2A deubiquitinase MYSM1. We demonstrated that MYSM1 is required for NK cell maturation but not for NK lineage specification and commitment. We also found that MYSM1 intrinsically controls this NK cell maturation. Mechanistic studies revealed that the expression of transcription factor, inhibitor of DNA-binding protein (ID2), a critical factor for NK cell development, is impaired in Mysm1(-/-) NK cells. MYSM1 interacts with nuclear factor IL-3 (NFIL3, also known as E4BP4), a critical factor for mouse NK cell development, and the recruitment of nuclear factor Il-3 to the ID2 locus is dependent on MYSM1. Further, we observed that MYSM1 is involved in maintaining an active chromatin at the ID2 locus to promote NK cell development. Hence this study demonstrates the critical epigenetic regulation of NK cell development by the histone H2A deubiquitinase MYSM1 through the transcriptional control of transcription factors important for NK cell development.
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