Skip to main content
Open Access Publications from the University of California


UC San Francisco Electronic Theses and Dissertations bannerUCSF

Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment


The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. Through ENU mutagenesis screening, we identified a mouse mutant, bloto, characterized by a deficiency in naïve T cells. The causative genetic lesion was identified as a hypomorphic mutation in the zinc finger protein Zfp335. Zfp335bloto/bloto mice had a paucity of naïve T lymphocytes due to a cell-intrinsic defect in mature thymocytes, as well as in peripheral T cells that have recently undergone thymic egress. The T cell defect in Zfp335bloto/bloto mice could not be explained by altered thymic selection, proliferation or Bcl2-dependent survival. ChIP-seq analysis revealed that Zfp335 binds primarily to promoter regions, and we identified a set of target genes in thymocytes that are enriched in categories related to protein metabolism, mitochondrial function, and transcriptional regulation. Our analysis also showed that Zfp335bloto occupancy at a subset of sites was significantly decreased, and that this reduced binding correlated with deregulated target gene expression. Restoring the expression of one target, Ankle2, partially rescued T cell maturation. Finally, we identified a new DNA recognition motif and demonstrated that it was bound by Zfp335 in vitro. We suggest that Zfp335 binds directly to DNA in a sequence-specific manner to control gene transcription and in doing so, functions as an essential regulator of late-stage intrathymic and post-thymic T cell maturation.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View