scholarly journals A looping-based model for quenching repression

2016 ◽  
Author(s):  
Y. Pollak ◽  
S. Goldberg ◽  
R. Amit

AbstractWe model the regulatory role of proteins bound to looped DNA using a simulation in which dsDNA is represented as a self-avoiding chain, and proteins as spherical protrusions. We simu-late long self-avoiding chains using a sequential importance sampling Monte-Carlo algorithm, and compute the probabilities for chain looping with and without a protrusion. We find that a protrusion near one of the chain’s termini reduces the probability of looping, even for chains much longer than the protrusion–chain-terminus distance. This effect increases with protrusion size, and decreases with protrusion-terminus distance. The reduced probability of looping can be explained via an eclipse-like model, which provides a novel inhibitory mechanism. We test the eclipse model on two possible transcription-factor occupancy states of theeve3/7 enhancer, and show that it provides a possible explanation for the experimentally-observedevestripe 3 and 7 expression patterns.The authors declare no conflict of interests

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 873
Author(s):  
Shahrbanou Hosseini ◽  
Armin Otto Schmitt ◽  
Jens Tetens ◽  
Bertram Brenig ◽  
Henner Simianer ◽  
...  

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.


Author(s):  
Stephen Wu ◽  
Panagiotis Angelikopoulos ◽  
Costas Papadimitriou ◽  
Petros Koumoutsakos

The transitional Markov chain Monte Carlo (TMCMC) is one of the efficient algorithms for performing Markov chain Monte Carlo (MCMC) in the context of Bayesian uncertainty quantification in parallel computing architectures. However, the features that are associated with its efficient sampling are also responsible for its introducing of bias in the sampling. We demonstrate that the Markov chains of each subsample in TMCMC may result in uneven chain lengths that distort the intermediate target distributions and introduce bias accumulation in each stage of the TMCMC algorithm. We remedy this drawback of TMCMC by proposing uniform chain lengths, with or without burn-in, so that the algorithm emphasizes sequential importance sampling (SIS) over MCMC. The proposed Bayesian annealed sequential importance sampling (BASIS) removes the bias of the original TMCMC and at the same time increases its parallel efficiency. We demonstrate the advantages and drawbacks of BASIS in modeling of bridge dynamics using finite elements and a disk-wall collision using discrete element methods.


Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 575 ◽  
Author(s):  
Naisu Yang ◽  
Bohao Zhao ◽  
Shuaishuai Hu ◽  
Zhiyuan Bao ◽  
Ming Liu ◽  
...  

The naturally colorful fur of the Rex rabbit is becoming increasingly popular in the modern textile market. Our previous study found that POU class 2 homeobox 1 gene (POU2F1) potentially affects the expression of genes involved in fur color formation in the Rex rabbit, but the function and regulation of POU2F1 has not been reported. In this study, the expression patterns of POU2F1 in Rex rabbits of various colors, as well as in different organs, were analyzed by RT-qPCR. Interference and overexpression of POU2F1 were used to identify the potential effects of POU2F1 on other genes related to fur color formation. The results show that the levels of POU2F1 expression were significantly higher in the dorsal skin of the brown and protein yellow Rex rabbits, compared with that of the black one. POU2F1 mRNAs were widespread in the tissues examined in this study and showed the highest level in the lungs. By transfecting rabbit melanocytes with an POU2F1-overexpression plasmid, we found that the POU2F1 protein was located at the nucleus, and the protein showed the classic characteristics of a transcription factor. In addition, abnormal expression of POU2F1 significantly affected the expression of pigmentation-related genes, including SLC7A11, MITF, SLC24A5, MC1R, and ASIP, revealing the regulatory roles of POU2F1 on pigmentation. The results provide the basis for further exploration of the role of POU2F1 in fur color formation of the Rex rabbit.


2014 ◽  
Author(s):  
Matthew Maurano ◽  
Hao Wang ◽  
Sam John ◽  
Anthony Shafer ◽  
Theresa Canfield ◽  
...  

The nuclear genome of every cell harbors millions of unoccupied transcription factor (TF) recognition sequences that harbor methylated cytosines. Although DNA methylation is commonly invoked as a repressive mechanism, the extent to which it actively silences specific TF occupancy sites is unknown. To define the role of DNA methylation in modulating TF binding, we quantified the effect of DNA methyltransferase abrogation on the occupancy patterns of a ubiquitous TF capable of autonomous binding to its target sites in chromatin (CTCF). Here we show that the vast majority of unoccupied, methylated CTCF recognition sequences remain unbound upon depletion of DNA methylation. Rather, methylation-regulated binding is restricted to a small fraction of elements that exhibit high intrinsic variability in CTCF occupancy across cell types. Our results suggest that DNA methylation is not a major groundskeeper of genomic transcription factor occupancy landscapes, but rather a specialized mechanism for stabilizing epigenetically labile sites.


2007 ◽  
Vol 27 (24) ◽  
pp. 8571-8582 ◽  
Author(s):  
Pieter Fokko van Loo ◽  
Edris A. F. Mahtab ◽  
Lambertus J. Wisse ◽  
Jun Hou ◽  
Frank Grosveld ◽  
...  

ABSTRACT Mice lacking the zinc finger transcription factor specificity protein 3 (Sp3) die prenatally in the C57BL/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at embryonic day 10.5 (E10.5), and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analyzed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. Chromatin immunoprecipitation analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small-molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development and suggest that it has a crucial role in myocardial differentiation.


Cell Reports ◽  
2015 ◽  
Vol 12 (7) ◽  
pp. 1184-1195 ◽  
Author(s):  
Matthew T. Maurano ◽  
Hao Wang ◽  
Sam John ◽  
Anthony Shafer ◽  
Theresa Canfield ◽  
...  

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.

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