Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes.
Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counter-regulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and menin-binding downstream of the transcription start site was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and menin cooccupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Atsushi
A
Onodera
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Damon J
DJ
Tumes
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Yukiko
Y
Watanabe
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Kiyoshi
K
Hirahara
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Atsushi
A
Kaneda
Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Fumihiro
F
Sugiyama
Laboratory of Functional Genomics, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwanoha, Kashiwa, Chiba, Japan.
Yutaka
Y
Suzuki
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan AMED-CREST, AMED, Inohana, Chuo-ku, Chiba, Japan tnakayama@faculty.chiba-u.jp.
Toshinori
T
Nakayama
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D016678:Genome; D008810:Mice, Inbred C57BL; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2