POSITIVE AND NEGATIVE REGULATION OF THE CARDIOVASCULAR TRANSCRIPTION FACTOR KLF5 BY THE COACTIVATOR/ACETYLASE P300 AND THE ONCOGENIC REGULATOR/NUCLEOSOME ASSEMBLY FACTOR SET BY INTERACTION AND ACETYLATION—IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION AT THE CHROMATIN LEVEL

2004 ◽  
Vol 13 (3) ◽  
pp. 10
Author(s):  
Toru Suzuki ◽  
Saku Miyamoto ◽  
Shinsuke Muto ◽  
Kenichi Aizawa ◽  
Masami Horikoshi ◽  
...  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.


Methods ◽  
2017 ◽  
Vol 126 ◽  
pp. 1-2 ◽  
Author(s):  
Howard D. Lipshitz ◽  
Julie M. Claycomb ◽  
Craig A. Smibert

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1012-1017 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Henry Kronenberg

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.


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