scholarly journals Alternative promoters and repetitive DNA elements define the species-dependent tissue-specific expression of the FMO1 genes of human and mouse

2007 ◽  
Vol 406 (3) ◽  
pp. 491-499 ◽  
Author(s):  
Elizabeth A. Shephard ◽  
Pritpal Chandan ◽  
Milena Stevanovic-Walker ◽  
Mina Edwards ◽  
Ian R. Phillips
Keyword(s):  
Reporter Gene ◽  
Adult Mouse ◽  
Direct Repeat ◽  
Mouse Gene ◽  
Gene Activity ◽  
Upstream Sequence ◽  
Alternative Promoters ◽  
Specific Expression ◽  
Tissue Specific ◽  
Reporter Gene Activity

In humans, expression of the FMO1 (flavin-containing mono-oxygenase 1) gene is silenced postnatally in liver, but not kidney. In adult mouse, however, the gene is active in both tissues. We investigated the basis of this species-dependent tissue-specific transcription of FMO1. Our results indicate the use of three alternative promoters. Transcription of the gene in fetal human and adult mouse liver is exclusively from the P0 promoter, whereas in extra-hepatic tissues of both species, P1 and P2 are active. Reporter gene assays showed that the proximal P0 promoters of human (hFMO1) and mouse (mFmo1) genes are equally effective. However, sequences upstream (−2955 to −506) of the proximal P0 of mFmo1 increased reporter gene activity 3-fold, whereas hFMO1 upstream sequences (−3027 to −541) decreased reporter gene activity by 75%. Replacement of the upstream sequence of human P0 with the upstream sequence of mouse P0 increased activity of the human proximal P0 8-fold. Species-specific repetitive elements are present immediately upstream of the proximal P0 promoters. The human gene contains five LINE (long-interspersed nuclear element)-1-like elements, whereas the mouse gene contains a poly A region, an 80-bp direct repeat, an LTR (long terminal repeat), a SINE (short-interspersed nuclear element) and a poly T tract. The rat and rabbit FMO1 genes, which are expressed in adult liver, lack some (rat) or all (rabbit) of the elements upstream of mouse P0. Thus silencing of FMO1 in adult human liver is due apparently to the presence upstream of the proximal P0 of L1 (LINE-1) elements rather than the absence of retrotransposons similar to those found in the mouse gene.

scholarly journals The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4395-4405 ◽  
Author(s):  
Päivi Pihlajamaa ◽  
Fu-Ping Zhang ◽  
Lilli Saarinen ◽  
Laura Mikkonen ◽  
Sampsa Hautaniemi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Reporter Gene ◽  
Gene Activity ◽  
Luciferase Expression ◽  
Experimental Conditions ◽  
Tissue Specific ◽  
Reporter Gene Activity ◽  
Mouse Tissues

To enable studies of androgen signaling in different tissues in vivo, we generated an androgen receptor (AR) reporter mouse line by inserting a luciferase gene construct into the murine genome. The construct is driven by four copies of androgen-responsive elements from the mouse sex-limited protein gene (slp-HRE2) and a minimal thymidine kinase promoter. Luciferase activity was readily measurable in a number of murine tissues, including prostate, lung, testis, brain, and skeletal muscle, and testosterone administration elicited a significant increase in reporter gene activity in these tissues. Consumption of isoflavonoid genistein is linked to reduced risk of prostate cancer, but direct effects of genistein on the AR pathway are not well understood. To examine androgen-modulating activity of genistein in vivo, male mice received daily doses of genistein (10 mg/kg) for 5 d. In intact males, genistein was antiandrogenic in testis, prostate, and brain, and it attenuated reporter gene activity by 50–80%. In castrated males, genistein exhibited significant androgen agonistic activity in prostate and brain by increasing reporter gene activity over 2-fold in both tissues. No antiandrogenic action was seen in lung or skeletal muscle of intact males. Gene expression profiling of the murine prostate under the same experimental conditions revealed that genistein modulates androgen-dependent transcription program in prostate in a fashion similar to that observed in reporter mice by luciferase expression. In conclusion, genistein is a partial androgen agonist/antagonist in some but not in all mouse tissues and should be considered as a tissue-specific AR modulator.

In vitro and in vivo analysis of murine lipoprotein lipase gene promoter: tissue-specific expression

1995 ◽  
Vol 268 (2) ◽  
pp. E213-E218 ◽  
Author(s):  
J. M. Gimble ◽  
X. Hua ◽  
F. Wanker ◽  
C. Morgan ◽  
C. Robinson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lipoprotein Lipase ◽  
Reporter Gene ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Brown Adipose ◽  
Octamer Motif

Lipoprotein lipase, an enzyme of central importance to lipid metabolism, is most abundant in adipose tissues, cardiac and skeletal muscle, and portions of the brain. The current work examined the murine lipoprotein lipase promoter using transient transfection, gel-retention analyses, and transgenic mice. Maximum expression of the luciferase reporter gene in transfected cells was observed with -101 bp of the promoter. Nuclear extracts from tissues expressing lipoprotein lipase contained DNA binding proteins that recognize the CCAAT box (-64 bp) and an octamer motif (-46 bp); this combination of factors was absent in nonexpressing tissues. Transgenic mice from three of five founders prepared with -1,824-bp promoter constructs expressed the luciferase reporter gene at highest levels in brown adipose tissue and brain. These findings suggest that the -1,824-bp promoter region contains sequence elements responsible for the tissue-specific transcription of lipoprotein lipase in vivo.

Analysis of the Alternative Promoters that Regulate Tissue-Specific Expression of Human Aromatic l-Amino Acid Decarboxylase

2002 ◽  
Vol 64 (2) ◽  
pp. 514-524 ◽  
Author(s):  
Chiho Sumi-Ichinose ◽  
Seiko Hasegawa ◽  
Hiroshi Ichinose ◽  
Hirohide Sawada ◽  
Kazuto Kobayashi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Decarboxylase ◽  
Alternative Promoters ◽  
Specific Expression ◽  
Tissue Specific ◽  
Amino Acid Decarboxylase ◽  
Tissue Specific Expression

Isotopic Assays for Reporter Gene Activity

2001 ◽  
Vol 63 (1) ◽  
Author(s):  
Robert E. Kingston ◽  
Jen Sheen ◽  
David Moore
Keyword(s):  
Reporter Gene ◽  
Gene Activity ◽  
Reporter Gene Activity

scholarly journals Human Serum Induces Streptococcal C5a Peptidase Expression

2009 ◽  
Vol 77 (9) ◽  
pp. 3817-3825 ◽  
Author(s):  
Ute Gleich-Theurer ◽  
Simone Aymanns ◽  
Gregor Haas ◽  
Stefanie Mauerer ◽  
Julia Vogt ◽  
...  
Keyword(s):  
Human Serum ◽  
Reporter Gene ◽  
Bovine Serum ◽  
Calf Serum ◽  
Gene Activity ◽  
Pcr Analysis ◽  
Reporter Gene Activity ◽  
Reverse Transcription Pcr ◽  
Bovine Strain ◽  
Human Infections

ABSTRACTStreptococcus agalactiaeis a major pathogen in humans and animals. Virulence factors are often associated with mobile genetic elements, and their expression can be modulated by host factors.S. agalactiaeharbors the genes for C5a peptidase (scpB) and Lmb on a composite transposon structure which is absent in many bovine isolates. To investigate whether these genes participate in the adaptation to human hosts, we determined the influence of human and bovine serum on the promoter activity ofscpBandlmbby using fluorescence-activated cell sorter analysis. Culture in the presence of 1 to 50% human serum resulted in a dose-dependent induction of reporter gene activity forscpBbut notlmb. Reporter gene activity was, however, unchanged following growth in fetal calf serum. Interestingly, a bovine strain did not display any induction ofscpBby either bovine or human serum. Reverse transcription-PCR analysis was used to confirm differential induction ofscpBinS. agalactiaeand showed a similar induction of theStreptococcus pyogenesC5a peptidase genescpAby human but not bovine serum. The specific induction of the streptococcal C5a peptidase by human serum corresponds to the absence ofscpBin many bovineS. agalactiaeisolates and underlines the importance of this virulence factor for human infections.

scholarly journals DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67925 ◽  
Author(s):  
Erling A. Hoivik ◽  
Solveig L. Witsoe ◽  
Inger R. Bergheim ◽  
Yunjian Xu ◽  
Ida Jakobsson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alternative Promoters ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression
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