scholarly journals Genome-wide and parental allele-specific analysis of CTCF and cohesin DNA binding in mouse brain reveals a tissue-specific binding pattern and an association with imprinted differentially methylated regions

2013 ◽  
Vol 23 (10) ◽  
pp. 1624-1635 ◽  
Author(s):  
A. R. Prickett ◽  
N. Barkas ◽  
R. B. McCole ◽  
S. Hughes ◽  
S. M. Amante ◽  
...  
Keyword(s):  
Dna Binding ◽  
Mouse Brain ◽  
Specific Binding ◽  
Binding Pattern ◽  
Differentially Methylated Regions ◽  
Tissue Specific ◽  
Parental Allele ◽  
Genome Wide ◽  
Specific Analysis ◽  
Allele Specific

scholarly journals Patterns of genome-wide allele-specific expression in hybrid rice and the implications on the genetic basis of heterosis

2019 ◽  
Vol 116 (12) ◽  
pp. 5653-5658 ◽  
Author(s):  
Lin Shao ◽  
Feng Xing ◽  
Conghao Xu ◽  
Qinghua Zhang ◽  
Jian Che ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Parental Allele ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Allele Specific

Utilization of heterosis has greatly increased the productivity of many crops worldwide. Although tremendous progress has been made in characterizing the genetic basis of heterosis using genomic technologies, molecular mechanisms underlying the genetic components are much less understood. Allele-specific expression (ASE), or imbalance between the expression levels of two parental alleles in the hybrid, has been suggested as a mechanism of heterosis. Here, we performed a genome-wide analysis of ASE by comparing the read ratios of the parental alleles in RNA-sequencing data of an elite rice hybrid and its parents using three tissues from plants grown under four conditions. The analysis identified a total of 3,270 genes showing ASE (ASEGs) in various ways, which can be classified into two patterns: consistent ASEGs such that the ASE was biased toward one parental allele in all tissues/conditions, and inconsistent ASEGs such that ASE was found in some but not all tissues/conditions, including direction-shifting ASEGs in which the ASE was biased toward one parental allele in some tissues/conditions while toward the other parental allele in other tissues/conditions. The results suggested that these patterns may have distinct implications in the genetic basis of heterosis: The consistent ASEGs may cause partial to full dominance effects on the traits that they regulate, and direction-shifting ASEGs may cause overdominance. We also showed that ASEGs were significantly enriched in genomic regions that were differentially selected during rice breeding. These ASEGs provide an index of the genes for future pursuit of the genetic and molecular mechanism of heterosis.

scholarly journals Critical DNA Binding Interactions of the Insulator Protein CTCF

2007 ◽  
Vol 282 (46) ◽  
pp. 33336-33345 ◽  
Author(s):  
Mario Renda ◽  
Ilaria Baglivo ◽  
Bonnie Burgess-Beusse ◽  
Sabrina Esposito ◽  
Roberto Fattorusso ◽  
...  
Keyword(s):  
Dna Binding ◽  
Large Scale ◽  
Specific Binding ◽  
Zinc Fingers ◽  
Dna Interaction ◽  
Ctcf Binding ◽  
Specific Expression ◽  
Binding Factor ◽  
Allele Specific ◽  
Enhancer Blocking

The DNA-binding protein CTCF (CCCTC binding factor) mediates enhancer blocking insulation at sites throughout the genome and plays an important role in regulating allele-specific expression at the Igf2/H19 locus and at other imprinted loci. Evidence is also accumulating that CTCF is involved in large scale organization of genomic chromatin. Although CTCF has 11 zinc fingers, we show here that only 4 of these are essential to strong binding and that they recognize a core 12-bp DNA sequence common to most CTCF sites. By deleting individual fingers and mutating individual sites, we determined the orientation of binding. Furthermore, we were able to identify the specific finger and its point of DNA interaction that are responsible for the loss of CTCF binding when CpG residues are methylated in the imprinted Igf2/H19 locus. This single interaction appears to be critical for allele-specific binding and insulation by CTCF.

scholarly journals Mitotic chromosome binding predicts transcription factor properties in interphase

2018 ◽  
Author(s):  
Mahé Raccaud ◽  
Andrea B. Alber ◽  
Elias T. Friman ◽  
Harsha Agarwal ◽  
Cédric Deluz ◽  
...  
Keyword(s):  
Dna Binding ◽  
Single Molecule ◽  
Mitotic Chromosome ◽  
Specific Binding ◽  
Site Occupancy ◽  
Chromatin Accessibility ◽  
Live Cells ◽  
Specific Binding Sites ◽  
Genome Wide ◽  
Chromosome Binding

SummaryMammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding affinity. How these properties affect the ability of TFs to occupy their specific binding sites in the genome and modify the epigenetic landscape is unclear. Here we combined live cell quantitative measurements of mitotic chromosome binding (MCB) of 502 TFs, measurements of TF mobility by fluorescence recovery after photobleaching, single molecule imaging of DNA binding in live cells, and genome-wide mapping of TF binding and chromatin accessibility. MCB scaled with interphase properties such as association with DNA-rich compartments, mobility, as well as large differences in genome-wide specific site occupancy that correlated with TF impact on chromatin accessibility. As MCB is largely mediated by electrostatic, non-specific TF-DNA interactions, our data suggests that non-specific DNA binding of TFs enhances their search for specific sites and thereby their impact on the accessible chromatin landscape.

scholarly journals Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA

2018 ◽  
Author(s):  
Ei-Wen Yang ◽  
Jae Hoon Bahn ◽  
Esther Yun-Hua Hsiao ◽  
Boon Xin Tan ◽  
Yiwei Sun ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Specific Binding ◽  
Specific Protein ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Allele Specific ◽  
Rna Interaction

AbstractAllele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants influencing RNA processing and gene expression phenotypes. Recently, genome-wide detection of in vivo binding sites of RNA binding proteins (RBPs) is greatly facilitated by the enhanced UV crosslinking and immunoprecipitation (eCLIP) protocol. Hundreds of eCLIP-Seq data sets were generated from HepG2 and K562 cells during the ENCODE3 phase. These data afford a valuable opportunity to examine allele-specific binding (ASB) of RBPs. To this end, we developed a new computational algorithm, called BEAPR (Binding Estimation of Allele-specific Protein-RNA interaction). In identifying statistically significant ASB sites, BEAPR takes into account UV cross-linking induced sequence propensity and technical variations between replicated experiments. Using simulated data and actual eCLIP-Seq data, we show that BEAPR largely outperforms often-used methods Chi-Squared test and Fisher’s Exact test. Importantly, BEAPR overcomes the inherent over-dispersion problem of the other methods. Complemented by experimental validations, we demonstrate that ASB events are significantly associated with genetic regulation of splicing and mRNA abundance, supporting the usage of this method to pinpoint functional genetic variants in post-transcriptional gene regulation. Many variants with ASB patterns of RBPs were found as genetic variants with cancer or other disease relevance. About 38% of ASB variants were in linkage disequilibrium with single nucleotide polymorphisms from genome-wide association studies. Overall, our results suggest that BEAPR is an effective method to reveal ASB patterns in eCLIP and can inform functional interpretation of disease-related genetic variants.

scholarly journals An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs)

2008 ◽  
Vol 18 (9) ◽  
pp. 1518-1529 ◽  
Author(s):  
V. K. Rakyan ◽  
T. A. Down ◽  
N. P. Thorne ◽  
P. Flicek ◽  
E. Kulesha ◽  
...  
Keyword(s):  
Human Tissue ◽  
Differentially Methylated Regions ◽  
Tissue Specific ◽  
Genome Wide
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