PMID- 24980046 OWN - NLM STAT- MEDLINE DCOM- 20140922 LR - 20211021 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 211 IP - 8 DP - 2014 Jul 28 TI - ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. PG - 1623-35 LID - 10.1084/jem.20132121 [doi] AB - 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. CI - (c) 2014 Ghosh et al. FAU - Ghosh, Hiyaa S AU - Ghosh HS AD - 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. FAU - Ceribelli, Michele AU - Ceribelli M AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. FAU - Matos, Ines AU - Matos I AD - 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. FAU - Lazarovici, Allan AU - Lazarovici A AD - 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. FAU - Bussemaker, Harmen J AU - Bussemaker HJ AD - 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. FAU - Lasorella, Anna AU - Lasorella A AD - 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. FAU - Hiebert, Scott W AU - Hiebert SW AD - Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232. FAU - Liu, Kang AU - Liu K AD - 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. FAU - Staudt, Louis M AU - Staudt LM AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. FAU - Reizis, Boris AU - Reizis B AD - 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. LA - eng SI - GEO/GSE43963 GR - R01 HG003008/HG/NHGRI NIH HHS/United States GR - HG003008/HG/NHGRI NIH HHS/United States GR - AI072571/AI/NIAID NIH HHS/United States GR - P30 AR044535/AR/NIAMS NIH HHS/United States GR - CA121852/CA/NCI NIH HHS/United States GR - R01 CA178030/CA/NCI NIH HHS/United States GR - UL1 TR000142/TR/NCATS NIH HHS/United States GR - R01 AI072571/AI/NIAID NIH HHS/United States GR - AR044535/AR/NIAMS NIH HHS/United States GR - R01 AI101251/AI/NIAID NIH HHS/United States GR - AI101251/AI/NIAID NIH HHS/United States GR - U54 CA121852/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140630 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Cbfa2t3 protein, mouse) RN - 0 (Chromatin) RN - 0 (E2F2 Transcription Factor) RN - 0 (Idb2 protein, mouse) RN - 0 (Inhibitor of Differentiation Protein 2) RN - 0 (Nuclear Proteins) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Base Sequence MH - Cell Differentiation MH - Cell Line MH - Cell Proliferation MH - Chromatin/metabolism MH - Dendritic Cells/*cytology/*metabolism MH - E2F2 Transcription Factor/metabolism MH - Gene Deletion MH - Humans MH - Inhibitor of Differentiation Protein 2/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Molecular Sequence Data MH - Nuclear Proteins/deficiency/*metabolism MH - Repressor Proteins/*metabolism MH - Stem Cells/metabolism MH - Transcription Factors/deficiency/*metabolism PMC - PMC4113936 EDAT- 2014/07/02 06:00 MHDA- 2014/09/23 06:00 PMCR- 2015/01/28 CRDT- 2014/07/02 06:00 PHST- 2014/07/02 06:00 [entrez] PHST- 2014/07/02 06:00 [pubmed] PHST- 2014/09/23 06:00 [medline] PHST- 2015/01/28 00:00 [pmc-release] AID - jem.20132121 [pii] AID - 20132121 [pii] AID - 10.1084/jem.20132121 [doi] PST - ppublish SO - J Exp Med. 2014 Jul 28;211(8):1623-35. doi: 10.1084/jem.20132121. Epub 2014 Jun 30.