Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoter

Transcription and epigenetic profile of the promoter, first exon and first intron of the human tyrosine hydroxylase gene

“…However, addition of genetic elements located upstream of the region (−194/+35) reduced transcriptional activity of recombinant human TH minimal promoters, indicating that a number of repressors of transcription are present inside the promoter (Kim et al, 2003b;Romano et al, 2005). Deletion analysis found a repressor of transcription in the region (−1,232/−1,210) of the human TH promoter (Kim et al, 2003b), whereas a study on evolutionary CRs among human, mouse and rat TH promoters identified another sequence encoding for repressor(s) of transcription in the region (−2,423/−2,327), which corresponds to CR-V (Romano et al, 2005). The transcriptional activity of a 6.3 kb human TH minimal promoter encoding for the region (−6,244/+35) was also very low (Fig.…”

“…Some studies shed useful insights in clarifying a confusing issue related to the comparison of TH gene regulation among various species, which is achieved through different mechanisms (Lenartowski and Goc, 2002;Lenartowski et al, 2003;Romano et al, 2005;Jin et al, 2006;Kelly et al, 2006). In this respect, a first important observation derived from the comparative analysis between the sequence of the human, mouse and rat TH promoters (Kessler et al, 2003;Romano et al, 2005), which revealed that the human TH promoter shares an approximate 46.6% degree of homology with the mouse TH promoter (Romano et al, 2005) and a 30% degree of homology with the rat TH promoter (Gandelman et al, 1990;Kim et al, 2003b). Only five short regions are evolutionarily conserved among the human, mouse and rat TH promoters (Kessler et al, 2003).…”

“…The degree of homology between the human and mouse TH promoters is about 46.6% (determined with a Clustalx program; Romano et al, 2005), whereas the human and rat TH promoters share only a 30% degree of homology (Gandelman et al, 1990;Kim et al, 2003b). The five CRs were placed upstream of the first-194 bp from the transcription start of the human TH promoter and the first 35 bp of the untranslated messenger RNA leader of the human TH gene (Romano et al, 2005).…”

“…These studies focused mainly on the human (Kessler et al, 2003;Romano et al, 2005;Jin et al, 2006), mouse (Kim et al, 2003a) and rat models (Gandelman et al, 1990;Kim et al, 2003b). In a previous report, a 13 kb DNA fragment containing the human TH promoter was isolated from a genomic DNA library, sequenced and utilized to generate both a transgenic animal model (Kessler et al, 2003) and a variety of recombinant minimal TH promoters assembled in a self-inactivating lentiviral vector system (Romano et al, 2005).…”

Novel pan-neuronal Cre-transgenic line for conditional ablation of genes in the nervous system

“…Similarly, under the control of the L7/pcp-2 promoter, Cre recombinase was expressed in cerebellar Purkinje cells (Barski et al, 2000), whereas GABA(A) Ra6-Cre promoter directed Cre recombinase to granule cells in the cerebellum (Funfschilling and Reichardt, 2002). Additional mouse lines expressing Cre recombinase in the brain include neuronal progenitor specific nestin-Cre (Betz et al, 1996;Tronche et al, 1999), midbrain-and hindbrain-restricted En2-Cre (Zinyk et al, 1998), hippocampal and cerebral cortical neuron-restricted EMX1-Cre Jin et al, 2000), motoneuron-specific NF-L (the neurofilament light chain) -Cre (Schweizer et al, 2002), dopaminergic neuron-specific tyrosine hydroxylase (TH) (Kim et al, 2003), neocortex-and hippocampus-expressed D6-Cre (van den Bout et al, 2002), and sensory ganglia-specific Scn10a-Cre (Agarwal et al, 2004). In transgenic mice expressing the tamoxifeninducible Cre-ERT recombinase under the control of prion protein (PrP) promoter, temporally controlled Cre-ERT expression was found in various locations of the CNS (Weber et al, 2001).…”