A bifunctional genetic regulatory element of the rat dopamine beta-hydroxylase gene influences cell type specificity and second messenger-mediated transcription.

Shaskus, John; Greco, Dominique; Asnani, L P; Lewis, Elaine J.

doi:10.1016/s0021-9258(19)37035-8

Cited by 60 publications

(1 citation statement)

References 43 publications

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“…Activation of PKA has been shown previously to be a potent stimulator of TH transcription (Kim et al 1994;Lewis-Tuffin et al 2004). It also activates DBH transcription (McMahon and Sabban 1992;Shaskus et al 1992).…”

Section: Discussionmentioning

confidence: 83%

Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism

et al. 2008

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Classically, upon hypothalamic stimulation, adrenocorticotropic hormone (ACTH) is released from the pituitary and acts on melanocortin 2 receptors (MC2R) in the adrenal cortex, stimulating glucocorticoid synthesis and release. Our earlier studies suggested that ACTH might have a direct effect on sympathetic ganglia. To analyze further the involvement of ACTH in regulation of gene expression of norepinephrine (NE) biosynthetic enzymes, we examined the effect of bilateral adrenalectomy (ADX) of Sprague-Dawley male rats. Fourteen days post-ADX, as expected, plasma ACTH was elevated, and levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and MC2R mRNAs in superior cervical ganglia (SCG), and TH mRNA in locus coeruleus (LC) were increased compared with sham-operated animals. To determine effect of pulsatile elevation of ACTH, corticosterone pellets were implanted to ADX rats. Similar to immobilization (IMO) stress ACTH injections to these animals caused a rise in ACTH in plasma and triggered elevation of TH and DBH mRNAs in SCG and in LC with single and repeated daily injections, and MC2R mRNA in SCG with single injections. To study the effect of ACTH in isolated cells, primary cultures of rat SCG were transfected with TH and DBH promoter constructs and treated with ACTH. In agreement with the in vivo data, ACTH elevated their promoter activities similar to levels triggered by cyclic AMP analog. ACTH in the human SK-N-SH neuroblastoma cells increased TH and DBH promoter activity and endogenous DBH mRNA levels. The results show that ACTH can have a direct effect on transcription and gene expression of NE biosynthetic enzymes even without contribution of adrenal hormones.

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Section: Discussionmentioning

confidence: 83%

Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism

et al. 2008

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Retinoic acid induces cholinergic differentiation of cultured newborn rat sympathetic neurons

Berrard

Biguet

Houhou

et al. 1993

J of Neuroscience Research

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Many studies provide evidence that retinoic acid (RA), an endogenous derivative of vitamin A, plays a role in the development of the nervous system. We now report that RA controls the neurotransmitter phenotype of post-mitotic rat sympathetic neurons in cell culture. RA added to the culture medium increased the specific activity of choline acetyltransferase (ChAT) and the level of acetylcholine (ACh). Concomitantly, RA reduced the specific activities of two catecholamine synthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) and the level of norepinephrine (NE). After a 2 week treatment with 5 microM RA, ChAT was increased by 5-10 fold, whereas TH and DBH were decreased by 10-15 fold and 2-3 fold, respectively, as compared to sympathetic neurons grown in the absence of RA. The modulation of the activity of the three enzymes was dose-dependent and followed a similar time course. The decrease of TH expression was demonstrated to be due to a decreased number of TH molecules.

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The transcription factor CREMτ and cAMP regulate promoter activity of the Na,K‐ATPase α4 isoform

Rodova

Nguyen

Blanco

2006

Molecular Reproduction Devel

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The Na,K-ATPase is an essential enzyme of the plasma membrane that plays a key role in numerous cell processes that depend on the transcellular gradients of Na(+) and K(+). Among the various isoforms of the catalytic subunit of the Na,K-ATPase, alpha4 exhibits the most limited pattern of expression, being restricted to male germ cells. Activity of alpha4 is essential for sperm function, and alpha4 is upregulated during spermatogenesis. The present study addressed the transcriptional control of the human Na,K-ATPase alpha4 gene, ATP1A4. We describe that a 5' untranslated region of the ATP1A4 gene (designated -339/+480 based on the ATP1A4 transcription initiation site) has promoter activity in luciferase reporter assays. Computer analysis of this promoter region revealed consensus sites (CRE) for the cyclic AMP (cAMP) response element modulator (CREM). Accordingly, dibutyryl cAMP (db-cAMP) and ectopic expression of CREMtau, a testis specific splice variant of CREM were able to activate the ATP1A4 promoter driven expression of luciferase in HEK 293 T, JEG-3 and GC-1 cells. Further characterization of the effect of db-cAMP and CREMtau on deleted constructs of the ATP1A4 promoter (-339/+80, and +25/+480), and on the -339/+480 region carrying mutations in the CRE sites showed that db-cAMP and CREMtau effect required the CRE motif located 263 bp upstream the transcription initiation site. EMSA experiments confirmed the CRE sequence as a bonafide CREMtau binding site. These results constitute the first demonstration of the transcriptional control of ATP1A4 gene expression by cAMP and by CREMtau, a transcription factor essential for male germ cell gene expression.

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A bifunctional genetic regulatory element of the rat dopamine beta-hydroxylase gene influences cell type specificity and second messenger-mediated transcription.

Cited by 60 publications

References 43 publications

Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism

Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism

Retinoic acid induces cholinergic differentiation of cultured newborn rat sympathetic neurons

The transcription factor CREMτ and cAMP regulate promoter activity of the Na,K‐ATPase α4 isoform

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