Characterization of Two Novel Nuclear BTB/POZ Domain Zinc Finger Isoforms

Abstract

BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF L and HOF S , that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic progenitors as well as in differentiated glia. During embryonic development of the murine cerebral cortex, HOF expression is restricted to the hippocampal subdivision. Expression coincides with early differentiation of presumptive CA1 and CA3 pyramidal neurons and dentate gyrus granule cells, with a sharp decline in expression at the CA1/subicular border. By using bromodeoxyuridine labeling and immunohistochemistry, we show that HOF expression coincides with immature non-dividing cells and is down-regulated in differentiated cells, suggesting a role for HOF in hippocampal neurogenesis. Consistent with the postulated role of the POZ domain as a site for protein-protein interactions, both HOF isoforms are able to dimerize. The HOF zinc fingers bind specifically to the binding site for the related promyelocytic leukemia zinc finger protein as well as to a newly identified DNA sequence.

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

“…ZTBT20 targets hippocampal neurons as well as cerebellum granule cells [26], consistent with our observation of a high ZTBT20 expression in the hippocampal, cerebellum and white matter regions of the brain. Conditionally deleting ZBTB20 specifically in mature CA1 pyramidal neurons impairs long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents [27].…”

Hippocampal pyramidal cells: the reemergence of cortical lamination

“…Furthermore, the aggregation of superficial CA1 pyramidal cell depends on their developmental expression of Zbtb20 (Fig. 3f), a member of the BTB/POZ zinc finger family (Mitchelmore et al 2002), without which CA1 develops a cortex-like structure (Xie et al 2010). Misexpression of Zbtb20 in extrahippocampal neurons results in the aggregation of cells of the upper layers of adjacent subicular fields in a compact CA1-like superficial layer (Nielsen et al 2007, 2010).…”

Astroglial c-Myc Overexpression Predisposes Mice to Primary Malignant Gliomas

“…The fixed sections were preincubated 15 min in phosphate-buffered saline containing 2% bovine serum albumin to reduce background, and immunohistochemistry was carried out as previously described using phosphate-buffered saline with 2% bovine serum albumin as the antibody diluent (24). The primary antibodies used at 1:100 dilution are mouse CNPase (Neomarkers), mouse NeuN (Chemicon), mouse GFAP (Chemicon), mouse VEGF (Santa Cruz), mouse PCNA (Sigma), rabbit GFAP (Sigma), rabbit c-Myc (Santa Cruz), rabbit cleaved caspase-3 (Cell Signaling Technology), and rabbit HOF antisera (25). For staining with sheep bromodeoxyuridine antisera (1:200 dilution; Research Diagnostics), the fixed sections were first treated for 30 s each with 2 M HCl and 0.1 M borate.…”

“…The HOF gene encodes a nuclear broad complex tramtrack bric-a-brac/poxvirus and zinc finger domain factor expressed in both developing and mature astrocytes as well as in reactive astroglia during brain pathology (25). As shown in Fig.…”