Transcription enhancer sequences: a novel regulatory element

1982 ◽  
Vol 7 (4) ◽  
pp. 124-125 ◽  
Author(s):  
W. Dynan ◽  
R. Tjian
1993 ◽  
Vol 13 (8) ◽  
pp. 4494-4504
Author(s):  
D Nitsch ◽  
G Schütz

Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.


Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 349-362 ◽  
Author(s):  
A.K. Hatzopoulos ◽  
A.S. Stoykova ◽  
J.R. Erselius ◽  
M. Goulding ◽  
T. Neuman ◽  
...  

A large family of tissue-specific nuclear proteins interact with the octamer motif ATTTGCAT, a transcriptional regulatory element found in the promoter and enhancer sequences of many genes. As a step towards elucidating the mechanism of this regulation, cDNA clones of the mouse Oct2 protein were isolated. One, called here Oct2b, encodes a larger variant of the previously described Oct2a proteins. The Oct2b cDNA has an insertion of 74 bp close to the 3′ end which creates an open reading frame distinct from Oct2a. As a result, the Oct2b protein has a carboxy end which is similar to that of the ubiquitous octamer-binding protein Oct1. Analysis of the Oct2 gene shows that Oct2a and Oct2b are differentially spliced products of the same gene. The insertion in the Oct2b cDNA results from the inclusion of an additional exon in the mRNA which would otherwise reside in an intron sequence of the Oct2a transcript. RNA analysis demonstrates that both Oct2a and 2b mRNAs are most abundant in B-cells but they are also expressed in a variety of tissues including brain, intestine, testis, kidney, as well as in embryos. Interestingly, the ratio of Oct2a and 2b varies among tissues. In situ hybridization studies during mouse embryogenesis show that the Oct2 gene is widely expressed in the developing nervous system. In contrast, expression in the adult brain is confined to very specific areas which include the suprachiasmatic and medial mammillary nuclei, hippocampus, olfactory tract and the olfactory bulb. Oct2 proteins are present in both neuronal and oligodendroglial cells, although they are more abundant in glial cells.


2021 ◽  
Author(s):  
Jake Leyhr ◽  
Laura Waldmann ◽  
Beata Filipek-Górniok ◽  
Hanqing Zhang ◽  
Amin Allalou ◽  
...  

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.


2011 ◽  
Vol 47 (2) ◽  
pp. 179-193 ◽  
Author(s):  
Aristides Lytras ◽  
Karen Detillieux ◽  
Peter A Cattini

The human chorionic somatomammotropin (CS) A and B genes (listed asCSH1andCSH2in the HUGO database) are highly expressed in placenta. A 241 bp potent enhancer, nucleotides (nts) 1–241, located at the 3′ end of theCS-Bgene (CS-Benh) stimulates promoter activity specifically in placental trophoblast cellsin vitro. Strong activity is exerted by a 23 bp element within the CS-Benh (nts 117–139), shown to interact with transcription enhancer factor (TEF) members of the transcription enhancer activator (TEA) DNA-binding domain-containing family. An identical TEF element is present in the homologous (97.5%) CS-Aenh; however, a few nucleotide differences suppress its activity. Previously, we identified regulatory sequences distinct from the TEF element within an 80 bp modulatory domain (nts 1–80) in the CS-Benh. Using structural and functional assays we now show that CCAAT/enhancer-binding protein (C/EBP) binding sites exist in the 80 bp modulatory domains of both enhancers, and an Elk-1 binding site exists in the modulatory domain of the CS-Aenh. C/EBPα or C/EBPβ strongly repressedCSp.CATactivity but stimulatedCSp.CAT.CS-Benhactivity. In contrast, the equivalentCS-Aenhancer sequences were unable to relieve promoter repression. Elk-1 overexpression also resulted in differential effects on the CS-Aenh versus CS-Benh. Finally, we provide evidence for the association of C/EBPβ with theCS-AandCS-Bgenes in human placental chromatin, including differential involvement of C/EBPβ with the CS-Aenh versus the CS-Benh, and therefore consistent with the notion that these are regions of regulatory significancein vivo. We conclude that members of the C/EBP and Ets families can differentially modulate CS-Benh and CS-Aenh activity.


1993 ◽  
Vol 13 (8) ◽  
pp. 4494-4504 ◽  
Author(s):  
D Nitsch ◽  
G Schütz

Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.


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