scholarly journals Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells

PLoS Genetics ◽  
2009 ◽  
Vol 5 (4) ◽  
pp. e1000446 ◽  
Author(s):  
Joana Sequeira-Mendes ◽  
Ramón Díaz-Uriarte ◽  
Anwyn Apedaile ◽  
Derek Huntley ◽  
Neil Brockdorff ◽  
...  
1999 ◽  
Vol 27 (3) ◽  
pp. 803-809 ◽  
Author(s):  
J. M. Larner ◽  
H. Lee ◽  
P. A. Dijkwel ◽  
R. D. Little ◽  
C. L. Schildkraut ◽  
...  

1995 ◽  
Vol 15 (6) ◽  
pp. 3301-3309 ◽  
Author(s):  
C Desdouets ◽  
G Matesic ◽  
C A Molina ◽  
N S Foulkes ◽  
P Sassone-Corsi ◽  
...  

Cyclin A is a pivotal regulatory protein which, in mammalian cells, is involved in the S phase of the cell cycle. Transcription of the human cyclin A gene is cell cycle regulated. We have investigated the role of the cyclic AMP (cAMP)-dependent signalling pathway in this cell cycle-dependent control. In human diploid fibroblasts (Hs 27), induction of cyclin A gene expression at G1/S is stimulated by 8-bromo-cAMP and suppressed by the protein kinase A inhibitor H89, which was found to delay S phase entry. Transfection experiments showed that the cyclin A promoter is inducible by activation of the adenylyl cyclase signalling pathway. Stimulation is mediated predominantly via a cAMP response element (CRE) located at positions -80 to -73 with respect to the transcription initiation site and is able to bind CRE-binding proteins and CRE modulators. Moreover, activation by phosphorylation of the activators CRE-binding proteins and CRE modulator tau and levels of the inducible cAMP early repressor are cell cycle regulated, which is consistent with the pattern of cyclin A inducibility by cAMP during the cell cycle. These results suggest that the CRE is, at least partly, implicated in stimulation of cyclin A transcription at G1/S.


2018 ◽  
Author(s):  
Andrew J Oldfield ◽  
Telmo Henriques ◽  
Dhirendra Kumar ◽  
Adam B. Burkholder ◽  
Senthilkumar Cinghu ◽  
...  

ABSTRACTFaithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription preinitiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results establish NF-Y as a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.


2021 ◽  
Vol 40 (19) ◽  
Author(s):  
Azadeh Sarfallah ◽  
Angelica Zamudio‐Ochoa ◽  
Michael Anikin ◽  
Dmitry Temiakov

2014 ◽  
Vol 88 (22) ◽  
pp. 13073-13085 ◽  
Author(s):  
Y.-L. Wu ◽  
C.-P. Wu ◽  
Y.-H. Huang ◽  
S.-P. Huang ◽  
H.-R. Lo ◽  
...  

2006 ◽  
Vol 80 (5) ◽  
pp. 2390-2395 ◽  
Author(s):  
Ryosuke Fujita ◽  
Takahiro Matsuyama ◽  
Junya Yamagishi ◽  
Ken Sahara ◽  
Shinichiro Asano ◽  
...  

ABSTRACT The gene expression of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) was examined in two types of mammalian cells, human HeLa14 and hamster BHK cells. DNA microarray analysis followed by reverse transcription-PCR identified at least 12 viral genes transcribed in both HeLa14 cells and BHK cells inoculated with AcMNPV. 5′ rapid amplification of cDNA ends was carried out to examine the transcriptional fidelity of these genes in HeLa14 cells. The transcription of ie-1, ie-0 and gp64 was initiated at a baculovirus early gene motif, CAGT, accompanied by a TATA motif. In addition, the same splicing observed for ie-0 mRNA in Sf9 cells occurred in HeLa14 cells. While the transcription initiation sites for pe38 and p6.9 were not located in the CAGT motif, most of them were in a typical eukaryotic RNA polymerase II promoter structure (a conventional TATA motif and/or an initiator). Interestingly, the expression of β-actin was upregulated in the mammalian cells inoculated with AcMNPV. Subsequent experiments using UV-inactivated virus confirmed the upregulation, suggesting that de novo synthesis of viral products is not required for the event. These results indicated that the AcMNPV genome acts as a template for transcription in mammalian cells through the usual infection pathway, though there is no evidence for the functional expression of viral genes at present.


2006 ◽  
Vol 80 (11) ◽  
pp. 5405-5412 ◽  
Author(s):  
Takashi Mino ◽  
Takeaki Hatono ◽  
Naoki Matsumoto ◽  
Tomoaki Mori ◽  
Yusuke Mineta ◽  
...  

ABSTRACT Recently, we demonstrated that plant DNA virus replication was inhibited in planta by using an artificial zinc finger protein (AZP) and created AZP-based transgenic plants resistant to DNA virus infection. Here we apply the AZP technology to the inhibition of replication of a mammalian DNA virus, human papillomavirus type 18 (HPV-18). Two AZPs, designated AZPHPV-1 and AZPHPV-2, were designed by using our nondegenerate recognition code table and were constructed to block binding of the HPV-18 E2 replication protein to the replication origin. Both of the newly designed AZPs had much higher affinities towards the replication origin than did the E2 protein, and they efficiently blocked E2 binding in vitro. In transient replication assays, both AZPs inhibited viral DNA replication, especially AZPHPV-2, which reduced the replication level to approximately 10%. We also demonstrated in transient replication assays, using plasmids with mutant replication origins, that AZPHPV-2 could precisely recognize the replication origin in mammalian cells. Thus, it was demonstrated that the AZP technology could be applied not only to plant DNA viruses but also to mammalian DNA viruses.


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