Engineered Deregulation of Expression in Yeast with Designed Hybrid‐Promoter Architectures in Coordination with Discovered Master Regulator Transcription Factor

2020 ◽  
Vol 4 (4) ◽  
pp. 1900172 ◽  
Author(s):  
Burcu Gündüz Ergün ◽  
İrem Demir ◽  
Tunçer H. Özdamar ◽  
Brigitte Gasser ◽  
Diethard Mattanovich ◽  
...  
Author(s):  
Fei Ge ◽  
Qi Pan ◽  
Yue Qin ◽  
Mengping Jia ◽  
Chengchao Ruan ◽  
...  

Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging.


FEBS Letters ◽  
2017 ◽  
Vol 591 (13) ◽  
pp. 2019-2031 ◽  
Author(s):  
Hirotaka Sugino ◽  
Takanori Usui ◽  
Tomohiro Shimada ◽  
Masahiro Nakano ◽  
Hiroshi Ogasawara ◽  
...  

2011 ◽  
Vol 124 (15) ◽  
pp. e1-e1
Author(s):  
E. Bolcun-Filas ◽  
L. A. Bannister ◽  
A. Barash ◽  
K. J. Schimenti ◽  
S. A. Hartford ◽  
...  

2021 ◽  
Author(s):  
Nicole L Nuckolls ◽  
Ananya Nidamangala Srinivasa ◽  
Anthony C Mok ◽  
María Angélica Bravo Núñez ◽  
Jeffrey J. Lange ◽  
...  

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtf poison protein and a Wtf antidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4 poison, but only the spores that inherit wtf4 receive a dose of Wtf4 antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4 poison transcript. This dual transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.


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