GSE43876
Mtg16 regulates E protein activity and lineage specification in dendritic cell development (ChIP-seq)
E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity. Overall design: Analysis of E2-2 and Mtg16 immunoprecipitated chromatin from CAL-1 cell line.