Molecular cloning and brain localization of HZF-2 alpha, a new member of the Rev-erb subfamily of orphan nuclear receptors.

We have isolated a novel cDNA homologous to the family of nuclear hormone receptors which we have designated hippocampal zinc finger-2 alpha (HZF-2 alpha). HZF-2 alpha encodes a protein 494 amino acids in length and predicted molecular size of 56 kD. HZF-2 alpha shares sequence similarities with orphan nuclear receptors related to thyroid hormone and retinoic acid receptors. An additional HZF-2 cDNA clone, HZF-2 beta, was isolated. HZF-2 beta differs from HZF-2 alpha in a nine-amino-acid region carboxyl to the DNA-binding domain thought to participate in enhancing the interaction of nuclear receptors with DNA. Northern blot analysis with a probe homologous to both HZF-2 alpha and beta identified two transcripts, sizes 4.4 and 5.5 kb in several rat tissues. HZF-2 alpha/beta mRNA levels are low in embryonic rat brain, increase during neonatal brain development and remain elevated in the adult rat brain. In situ hybridization analyses localized HZF-2 alpha/beta mRNA expression to all hippocampal subfields. Within the hippocampus heaviest expression was observed within the dentate gyrus. High levels of HZF-2 alpha/beta mRNA were also detected in Purkinje cells and the granular cell layer of the cerebellum. In summary, HZF-2 alpha/beta are novel orphan nuclear receptors which may play an important role in hormone-dependent aspects of developmental processes modulating hippocampal and cerebellar plasticity.