The BTB-ZF transcription factors

Abstract

The BTB-ZF (broad-complex, tramtrack and bric-à-brac--zinc finger) proteins are encoded by at least 49 genes in mouse and man and commonly serve as sequence-specific silencers of gene expression. This review will focus on the known physiological functions of mammalian BTB-ZF proteins, which include essential roles in the development of the immune system. We discuss their function in terminally differentiated lymphocytes and the progenitors that give rise to them, their action in hematopoietic malignancy and roles beyond the immune system.

Figure 1. Domain structure and phylogeny of 49 human BTB-ZF proteins. All contain a single BTB domain and between 2 and 14 C₂H₂ ZF domains, with PATZ1 and ZBTB24 also containing an AT-hook domain. Note that ZBTB12B is a pseudogene, ZBTB8OS does not encode a BTB-ZF protein, and that ANKFY1 has a FYVE-type rather than a C₂H₂ ZF domain. Amino acid sequences of each of the BTB-ZF proteins were obtained from Uniprot, and phylogenetic analysis was performed using Phylogeny.fr: (i) Amino acid sequences were aligned with Multiple Sequence Comparison by Log-Expectation (MUSCLE, v. 3.7; default settings). (ii) The maximum likelihood method in PhyML (v. 3.0, aLRT) was used to generate the phylogenetic tree from the multiple sequence alignment. The WAG substitution model was selected assuming an estimated proportion of invariant sites (of 0.000) and 4 gamma-distributed rate categories to account for rate heterogeneity across sites. The gamma shape parameter was estimated directly from the data (gamma = 1.158). Reliability for internal branch was assessed using the Approximate Likelihood Ratio Test (aLRT; SH-Like). (iii) Graphical representation of the phylogenetic tree was performed with TreeDyn (v. 198.3) in the radial style of DrawTree from the PHYLIP package (v. 3.66).

Figure 4. Collective display of mouse BTB-ZF gene expression data. Relative tissue-specific transcript expression data were obtained from BioGPS and are representative of multiple transcript probes where appropriate. Gray columns indicate hematopoietic tissues, while black columns are non-hematopoietic. pDC, plasmacytoid dendritic cell; BMDM, bone marrow-derived macrophage; LPS, lipopolysaccharide; GMP, granulocyte-monocyte progenitor; MEP, megakaryocyte-erythrocyte progenitor; HSC, hematopoietic stem cell.

Figure 2. Schematic of BTB-ZF protein functions in hematopoiesis and immunity. Labels outside cells represent a requirement for the BTB-ZF protein during development. Labels inside cells represent a requirement in effector function. See text for additional details.

Figure 3. Transcriptional circuits involving mammalian BTB-ZF proteins. Examples shown are from pathways established in mammalian primary cells, question marks indicate that a direct interaction is yet to be demonstrated. See text for additional details.