The 5′-flanking region of the human dopamine β-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice

1993 ◽  
Vol 17 (3-4) ◽  
pp. 239-244 ◽  
Author(s):  
Shinji Morita ◽  
Kazuto Kobayashi ◽  
Tomoko Mizuguchi ◽  
Keiki Yamada ◽  
Ikuko Nagatsu ◽  
...  
2004 ◽  
Vol 90 (6) ◽  
pp. 1445-1452 ◽  
Author(s):  
Renee Morris ◽  
Branwen S. Morgan ◽  
Trevor M. Lewis ◽  
Kerrie D. Pierce ◽  
Anthony Pisano ◽  
...  

2003 ◽  
Vol 370 (2) ◽  
pp. 557-566 ◽  
Author(s):  
Ying SUN ◽  
David P. WITTE ◽  
Peng JIN ◽  
Gregory A. GRABOWSKI

The expression of prosaposin is temporally and spatially regulated at transcriptional and post-translational levels. Transgenic mice with various 5′-flanking deletions of the prosaposin promoter fused to luciferase (LUC) reporters were used to define its temporal regulatory region. LUC expression in the transgenic mice carrying constructs with 234bp (234LUC), 310bp (310LUC) or 2400bp (2400LUC) of the 5′-flanking region was analysed in the central nervous system and eye throughout development. For 310LUC and 2400LUC, low-level LUC activity was maintained until embryonal day 18 in brain, eye and spinal cord. The peak level of LUC activity was at birth, with return to a plateau (1/3 of peak) throughout adulthood. Deletion of the region that included the retinoic acid-receptor-related orphan receptor (RORα)-binding site and sequence-specific transcription factor (Sp1) cluster sites (44—310bp) suppressed the peak of activity. By comparison, the peak level for 234LUC was shifted 2 weeks into neonatal life in the brain, but not in the eye, and no peak of activity was observed in the spinal cord. The endogenous prosaposin mRNA in eye, spinal cord and cerebellum had low-level expression before birth and continued to increase into adulthood. In cerebrum, the endogenous mRNA showed similar expression profile to constructs 310LUC, 2400LUC and 234LUC, with the peak expression at 1 week and a decreased level in adult. In the brain of the newborn, 2400LUC was highly expressed in the trigeminal ganglion and brain stem regions when compared with the generalized expression pattern for endogenous prosaposin mRNA. These results suggest that the modifiers (RORα- and Sp1-binding sites) residing within 310bp of the 5′-flanking region mediate developmental regulation in the central nervous system and eye. Additional regulatory elements outside the 5′ region of the 2400bp promoter fragment appear to be essential for the physiological control of the prosaposin locus.


2008 ◽  
Vol 28 (6) ◽  
pp. 1905-1914 ◽  
Author(s):  
Ramesh Chellappa ◽  
Shengguo Li ◽  
Sarah Pauley ◽  
Israt Jahan ◽  
Kangxin Jin ◽  
...  

ABSTRACT The development of the nervous system requires the concerted actions of multiple transcription factors, yet the molecular events leading to their expression remain poorly understood. Barhl1, a mammalian homeodomain transcription factor of the BarH class, is expressed by developing inner ear hair cells, cerebellar granule cells, precerebellar neurons, and collicular neurons. Targeted gene inactivation has demonstrated a crucial role for Barhl1 in the survival and/or migration of these sensory cells and neurons. Here we report the regulatory sequences of Barhl1 necessary for directing its proper spatiotemporal expression pattern in the inner ear and central nervous system (CNS). Using a transgenic approach, we have found that high-level and cell-specific expression of Barhl1 within the inner ear and CNS depends on both its 5′ promoter and 3′ enhancer sequences. Further transcriptional, binding, and mutational analyses of the 5′ promoter have identified two homeoprotein binding motifs that can be occupied and activated by Barhl1. Moreover, proper Barhl1 expression in inner ear hair cells and cerebellar and precerebellar neurons requires the presence of Atoh1. Together, these data delineate useful Barhl1 regulatory sequences that direct strong and specific gene expression to inner ear hair cells and CNS sensory neurons, establish a role for autoregulation in the maintenance of Barhl1 expression, and identify Atoh1 as a key upstream regulator.


Gene ◽  
2004 ◽  
Vol 337 ◽  
pp. 91-103 ◽  
Author(s):  
Hidehiko Sugino ◽  
Tomoko Toyama ◽  
Yusuke Taguchi ◽  
Shigeyuki Esumi ◽  
Mitsuhiro Miyazaki ◽  
...  

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