Screening rhythmic expression of lncRNA in liver tissue.

On March 8, the journal Nucleic Acid Research published a paper online entitled Class of circa longdian non-coding RNAs mark enhancers moduling long-range circadian gene regulation by Yan Jun Of the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences and the Institute of Neuroscience of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences.
the study revealed that a class of rhythmic expressions of long non-coded RNA (lncRNA) markes the genome's enhancers that can mediate long-range chromatin interactions, and that this interaction regulates the expression of rhythmic genes.
circadian rhythm is a 24-hour periodic physiological phenomenon that regulates many physiological and behavioral processes in animals by regulating gene expression at a variety of levels, including transcription levels and post-transcription levels.
lncRNA is a class of non-coding RNA longer than 200 bases that is highly tissue-specific and has been found to play a role in processes such as genomic imprints, cell cycles, tumor occurrence, and so on.
In the past, the regulation of rhythm genes mainly focused on protein-coding genes, although the lncRNA of individual rhythm expression was found, but there was a lack of systematic research on rhythmic lncRNA;
using liver tissue RNA-seq, the researchers systematically stitched together lncRNAs expressed in the liver and screened out lncRNAs expressed in rhythms through the day and night.
By analyzing the enhanced subregions of histoprotein-modified signal markers, it was found that rhythmic lncRNA was significantly rich in the enhanced subregions, showing an association between the two, and that these regions had binding points for two very important rhythm transcription factors, BMAL1 and REV-ERB alpha.
rhythm lncRNA in enhanced subregions is not only found in mouse livers, but has also been found in mouse pancreas and rat livers.
these rhythmic lncRNAs have very similar rhythmic phases and very high correlations with the expression of nearby genes through the day.
cell positioning of lnc-Crot and Crot based on the results of the fluorescence in-place hybridization experiment.
(B) heat map shows that there is no significant difference between the genes that interact with lnc-Crot on chromosome 5 from 4C-seq.
(C) working model diagram showing that the enhancers marked by rhythm lncRNA perform rhythmic regulation through long-range interaction, mediated in combination with the function of rhythm transcription factors on it.
by comparing the subcellular positioning of lncRNA with protein-coding genes, it was found that lncRNA was more rich in the nucleation of cells than protein-coding genes (as shown in Figure A), but lower than enhanced subRNAs (eRNAs).
addition, a comparative analysis of rhythm transcription groups in rats and mice found that although the sequence of lncRNA was less conservative, the site of rhythmlncRNA transcription was still tending to be conservative.
researchers found a candidate rhythm lncRNA, named lnc-Crot, using ring chromatin image capture technology (4C-seq) to find that the super-enhanced sub-region in which lnc-Crot is located interacts with many genes on chromatin over a long period of time (as shown in Figure B), many of which are involved in metabolic processes, and that the rhythm peaks are rich in time close to the peak point of lnc-Crot, indicating that these interactions interact with the gene's function and rhythmic expression.
further experiments in cell line were found that the enhancers of lnc-Crot mediated the regulatory function of rev-ERB alpha, a transcription factor that binds to it.
The study's systematic analysis of rhythm lncRNA by histological means revealed that rhythm lncRNA marks a class of active enhancers that regulate gene expression through long-range interactions that are relatively stable, but that the rhythmic transcription factors that bind to them achieve rhythmic regulation of genes (Figure C), and that the annotations of these rhythms lncRNA provide a basis for further exploration of their function in rhythms.
The work was mainly carried out under the guidance of researcher Yan Jun, by Fan Zenghua, Zhao Meng and others, and with the participation of Zhao Zhihu Research Group of the Academy of Military Medical Sciences and Gregor Eichele Group of the Institute of Biophysics and Chemistry of the German Magpies, supported by projects such as the Special Fund for Strategic Pilot Science and Technology of the Chinese Academy of Sciences (XDB02060006) and the National Natural Science Foundation (31571209,31370762).
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