title: ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
abstract: Dendritic cells (DCs) comprise two major subsets, the interferon (IFN)-producing plasmacytoid DCs (pDCs) and antigen-presenting classical DCs (cDCs). The development of pDCs is promoted by E protein transcription factor E2-2, whereas E protein antagonist Id2 is specifically absent from pDCs. Conversely, Id2 is prominently expressed in cDCs and promotes CD8(+) cDC development. The mechanisms that control the balance between E and Id proteins during DC subset specification remain unknown. We found that the loss of Mtg16, a transcriptional cofactor of the ETO protein family, profoundly impaired pDC development and pDC-dependent IFN response. The residual Mtg16-deficient pDCs showed aberrant phenotype, including the expression of myeloid marker CD11b. Conversely, the development of cDC progenitors (pre-DCs) and of CD8(+) cDCs was enhanced. Genome-wide expression and DNA-binding analysis identified Id2 as a direct target of Mtg16. Mtg16-deficient cDC progenitors and pDCs showed aberrant induction of Id2, and the deletion of Id2 facilitated the impaired development of Mtg16-deficient pDCs. Thus, Mtg16 promotes pDC differentiation and restricts cDC development in part by repressing Id2, revealing a cell-intrinsic mechanism that controls subset balance during DC development.
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Hiyaa S
authors: HS
authors: Ghosh
authors: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: Michele
authors: M
authors: Ceribelli
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Ines
authors: I
authors: Matos
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Allan
authors: A
authors: Lazarovici
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Harmen J
authors: HJ
authors: Bussemaker
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Anna
authors: A
authors: Lasorella
authors: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors: Scott W
authors: SW
authors: Hiebert
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
authors: Kang
authors: K
authors: Liu
authors: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: Louis M
authors: LM
authors: Staudt
authors: Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032 bvr2101@columbia.edu.
authors: Boris
authors: B
authors: Reizis
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D050703:E2F2 Transcription Factor / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: C117411:Cbfa2t3 protein, mouse; D002843:Chromatin; D050703:E2F2 Transcription Factor; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors