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Beschreibung

Zinc finger and BTB domain-containing protein 46 (UniProt Q86UZ6, also known as BTB-ZF protein expressed in effector lymphocytes, BTB/POZ domain-containing protein 4, BZEL, Classical dendritic cell-restricted zinc finger transcription factor zDC, Zinc finger protein 340) is encoded by the ZBTB46 (also known as BTBD4, ZNF340) gene (Gene ID 140685) in human. ZBTB46/ZNF340 is a broad complex, tramtrack, bric-a-brac and zinc finger (BTB-ZF) protein expressed in classical dendritic cells (cDCs), but not other immune cell populations, including plasmacytoid DCs, monocytes, or macrophages. Genome-wide ChIP-seq analysis reveals that ZBTB46/ZNF340 associates with more than 1,000 gene promoters and acts as a transcriptional repressor against many of these target genes. Zbtb46-knockout profoundly alters the cDC subset composition in the spleen in favor of CD8+ DCs, as well as upregulates activation pathways in steady-state cDCs, including elevated creb1 and MHC II expression, and enhances cDC production of vascular endothelial growth factor, leading to increased vascularization of skin-draining lymph nodes. Human ZBTB46/ZNF340 is a 589-a.a. protein containing a BTB domain (a.a. 31-99) and two C2H2-type Zinc fingers (a.a. 418-436, 446-468).