scholarly journals PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingwen Fang ◽  
Qing Ma ◽  
Ci Chu ◽  
Beibei Huang ◽  
Lingjie Li ◽  
...  

AbstractWe develop PIRCh-seq, a method which enables a comprehensive survey of chromatin-associated RNAs in a histone modification-specific manner. We identify hundreds of chromatin-associated RNAs in several cell types with substantially less contamination by nascent transcripts. Non-coding RNAs are found enriched on chromatin and are classified into functional groups based on the patterns of their association with specific histone modifications. We find single-stranded RNA bases are more chromatin-associated, and we discover hundreds of allele-specific RNA-chromatin interactions. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interactions.

2019 ◽  
Author(s):  
Jingwen Fang ◽  
Qing Ma ◽  
Ci Chu ◽  
Beibei Huang ◽  
Lingjie Li ◽  
...  

ABSTRACTMany long noncoding RNAs (lncRNAs) regulate gene transcription through binding to histone modification complexes. Therefore, a comprehensive study of nuclear RNAs in a histone modification-specific manner is critical to understand their regulatory mechanisms. Here we develop a method named Profiling Interacting RNAs on Chromatin by deep sequencing (PIRCh-seq), in which we profile chromatin-associated transcriptome in 5 different cell types using antibodies recognizing histone H3 and 6 distinct histone modifications associated with active or repressive chromatin states. PIRCh-seq identified chromatin-associated RNAs with substantially less contamination by nascent transcripts, as compared to existing methods. We classified chromatin-enriched lncRNAs into 6 functional groups based on the patterns of their association with specific histone modifications. LncRNAs were enriched with different chromatin modifications in different cell types, suggesting lncRNAs’ regulation may also be cell type-specific. By integrating profiles of RNA secondary structure and RNA m6A modification, we found that RNA bases which bind to chromatin tend to be more single stranded. We discovered hundreds of allele-specific RNA-chromatin interactions, nominating specific single nucleotide variants that alter RNA association with chromatin. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interaction.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seyed Ali Madani Tonekaboni ◽  
Benjamin Haibe-Kains ◽  
Mathieu Lupien

AbstractThe human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.


2021 ◽  
Vol 8 ◽  
Author(s):  
Tiqun Yang ◽  
Tianxin Long ◽  
Tailai Du ◽  
Yili Chen ◽  
Yugang Dong ◽  
...  

Cardiac remodeling occurs after the heart is exposed to stress, which is manifested by pathological processes such as cardiomyocyte hypertrophy and apoptosis, dendritic cells activation and cytokine secretion, proliferation and activation of fibroblasts, and finally leads to heart failure. Circular RNAs (circRNAs) are recently recognized as a specific type of non-coding RNAs that are expressed in different species, in different stages of development, and in different pathological conditions. Growing evidences have implicated that circRNAs play important regulatory roles in the pathogenesis of a variety of cardiovascular diseases. In this review, we summarize the biological origin, characteristics, functional classification of circRNAs and their regulatory functions in cardiomyocytes, endothelial cells, fibroblasts, immune cells, and exosomes in the pathogenesis of cardiac remodeling.


2007 ◽  
Vol 28 (1) ◽  
pp. 71-82 ◽  
Author(s):  
Raluca I. Verona ◽  
Joanne L. Thorvaldsen ◽  
Kimberly J. Reese ◽  
Marisa S. Bartolomei

ABSTRACT Genomic imprinting governs allele-specific gene expression in an epigenetically heritable manner. The characterization of histone modifications at imprinted gene loci is incomplete, and whether specific histone marks determine transcription or are dependent on it is not understood. Using chromatin immunoprecipitations, we examined in multiple cell types and in an allele-specific manner the active and repressive histone marks of several imprinted loci, including H19, KvDMR1, Snrpn promoter/exon 1, and IG-DMR imprinting control regions. Expressed alleles are enriched for specific actively modified histones, including H3 di- and trimethylated at Lys4 and acetylated histones H3 and H4, while their silent counterparts are associated with repressive marks such as H3 trimethylated at Lys9 alone or in combination with H3 trimethylated at Lys27 and H4/H2A symmetrically dimethylated at Arg3. At H19, allele-specific histone modifications occur throughout the entire locus, including nontranscribed regions such as the differentially methylated domain (DMD) as well as sequences in the H19 gene body that are not differentially methylated. Significantly, the presence of active marks at H19 depends on transcriptional activity and occurs even in the absence of the DMD. These findings suggest that histone modifications are dependent on the transcriptional status of imprinted alleles and illuminate epigenetic mechanisms of genomic imprinting.


2017 ◽  
Author(s):  
Kai Zhang ◽  
Mengchi Wang ◽  
Ying Zhao ◽  
Wei Wang

AbstractDynamic changes in the transcriptional regulatory circuit can influence the specification of distinct cell types. Numerous transcription factors (TFs) have been shown to function through dynamic rewiring during embryonic development but a comprehensive survey on the global regulatory network is still lacking. Here, we performed an integrated analysis of epigenomic and transcriptomic data to reveal key regulators from 2 cells to postnatal day 0 in mouse embryogenesis. We predicted 3D chromatin interactions including enhancer-promoter interactions in 12 tissues across 8 developmental stages, which facilitates linking TFs to their target genes for constructing genetic networks. To identify driver TFs particularly those not necessarily differentially expressed ones, we developed a new algorithm, dubbed as Taiji, to assess the global importance of TFs in development. Through comparative analysis across tissues and developmental stages, we systematically uncovered TFs that are critical for lineage-specific and stage-dependent tissue specification. Most interestingly, we have identified TF combinations that function in spatiotemporal order to form transcriptional waves regulating developmental progress and differentiation. Not only does our analysis provide the first comprehensive map of transcriptional regulatory circuits during mouse embryonic development, the identified novel regulators and the predicted 3D chromatin interactions also provide a valuable resource to guide further mechanistic studies.


Epigenomes ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 26
Author(s):  
Annalisa Fico ◽  
Luciano Di Croce ◽  
Maria R. Matarazzo

The epigenome refers to the entirety of DNA methylations, histone modifications, nucleosome occupancy, and coding and non-coding RNAs (and their modifications) in different cell types [...]


2018 ◽  
Vol 50 (10) ◽  
pp. 1474-1482 ◽  
Author(s):  
Jessime M. Kirk ◽  
Susan O. Kim ◽  
Kaoru Inoue ◽  
Matthew J. Smola ◽  
David M. Lee ◽  
...  

Physiotherapy ◽  
2013 ◽  
Vol 21 (3) ◽  
Author(s):  
Natalia Uścinowicz ◽  
Wojciech Seidel ◽  
Paweł Zostawa ◽  
Sebastian Klich

AbstractThe recent Olympic Games in London incited much interest in the competition of disabled athletes. Various people connected with swimming, including coaches and athletes, have speculated about the fairness of competitions of disabled athletes. A constant problem are the subjective methods of classification in disabled sport. Originally, athletes with disabilities were classified according to medical diagnosis. Due to the injustice which still affects the competitors, functional classification was created shortly after. In the present review, the authors show the anomalies in the structure of the classification. The presented discovery led to the suggestion to introduce objective methods, thanks to which it would be no longer necessary to rely on the subjective assessment of the classifier. According to the authors, while using objective methods does not completely rule out the possibility of fraud by disabled athletes in the classification process, it would certainly reduce their incidence. Some of the objective methods useful for the classification of disabled athletes are: posturography, evaluation of the muscle parameters, electrogoniometric assessment, surface electromyography, and analysis of kinematic parameters. These methods have provide objective evaluation in the diagnostic sense but only if they are used in tandem. The authors demonstrate the undeniable benefits of using objective methods. Unfortunately, there are not only advantages of such solution, there also several drawbacks to be found. The conclusion of the article is the statement by the authors that it is right to use objective methods which allow to further the most important rule in sport: fair-play.


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