Publications by authors named "Hsiao-Lin V Wang"

8 Publications

  • Page 1 of 1

Exposure to sevoflurane results in changes of transcription factor occupancy in sperm and inheritance of autism.

Biol Reprod 2021 May 12. Epub 2021 May 12.

Department of Human Genetics, Emory University School of Medicine, 615 Michael St, Atlanta, GA 30322, USA.

One in 54 children in the U.S. is diagnosed with Autism Spectrum Disorder (ASD). De novo germline and somatic mutations cannot account for all cases of ASD, suggesting that epigenetic alterations triggered by environmental exposures may be responsible for a subset of ASD cases. Human and animal studies have shown that exposure of the developing brain to general anesthetic (GA) agents can trigger neurodegeneration and neurobehavioral abnormalities but the effects of general anesthetics on the germ line have not been explored in detail. We exposed pregnant mice to sevoflurane during the time of embryonic development when the germ cells undergo epigenetic reprogramming and found that more than 38% of the directly exposed F1 animals exhibit impairments in anxiety and social interactions. Strikingly, 44-47% of the F2 and F3 animals, which were not directly exposed to sevoflurane, show the same behavioral problems. We performed ATAC-seq and identified more than 1200 differentially accessible sites in the sperm of F1 animals, 69 of which are also present in the sperm of F2 animals. These sites are located in regulatory regions of genes strongly associated with ASD, including Arid1b, Ntrk2, and Stmn2. These findings suggest that epimutations caused by exposing germ cells to sevoflurane can lead to ASD in the offspring, and this effect can be transmitted through the male germline inter and trans-generationally.
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http://dx.doi.org/10.1093/biolre/ioab097DOI Listing
May 2021

Seeing Is Believing: ORCA Allows Visualization of Three-Dimensional Genome Organization at Single-Cell Resolution.

Biochemistry 2019 08 12;58(33):3477-3479. Epub 2019 Aug 12.

Department of Biology , Emory University , 1510 Clifton Road Northeast , Atlanta , Georgia 30322 , United States.

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http://dx.doi.org/10.1021/acs.biochem.9b00611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702087PMC
August 2019

Novel mRNAs 3' end-associated -regulatory elements with epigenomic signatures of mammalian enhancers in the genome.

RNA 2019 10 16;25(10):1242-1258. Epub 2019 Jul 16.

Mycological Research Center, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.

The precise spatial and temporal control of gene expression requires the coordinated action of genomic -regulatory elements (CREs), including transcriptional enhancers. However, our knowledge of enhancers in plants remains rudimentary and only a few plant enhancers have been experimentally defined. Here, we screened the genome and identified >1900 unique candidate CREs that carry the genomic signatures of mammalian enhancers. These were termed putative enhancer-like elements (PEs). Nearly all PEs are intragenic and, unexpectedly, most associate with the 3' ends of protein-coding genes. PEs are hotspots for transcription factor binding and harbor motifs resembling cleavage/polyadenylation signals, potentially coupling 3' end processing to the transcriptional regulation of other genes. Hi-C data showed that 24% of PEs are located at regions that can interact intrachromosomally with other protein-coding genes and, surprisingly, many of these target genes interact with PEs through their 3' UTRs. Examination of the genomes of 1135 sequenced accessions showed that PEs are conserved. Our findings suggest that the identified PEs may serve as transcriptional enhancers and sites for mRNA 3' end processing, and constitute a novel group of CREs in .
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http://dx.doi.org/10.1261/rna.071209.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800480PMC
October 2019

An Overview of Methodologies in Studying lncRNAs in the High-Throughput Era: When Acronyms ATTACK!

Methods Mol Biol 2019 ;1933:1-30

Guangxi Key Laboratory of Sugarcane Biology, Guangxi University, Nanning, Guangxi, China.

The discovery of pervasive transcription in eukaryotic genomes provided one of many surprising (and perhaps most surprising) findings of the genomic era and led to the uncovering of a large number of previously unstudied transcriptional events. This pervasive transcription leads to the production of large numbers of noncoding RNAs (ncRNAs) and thus opened the window to study these diverse, abundant transcripts of unclear relevance and unknown function. Since that discovery, recent advances in high-throughput sequencing technologies have identified a large collection of ncRNAs, from microRNAs to long noncoding RNAs (lncRNAs). Subsequent discoveries have shown that many lncRNAs play important roles in various eukaryotic processes; these discoveries have profoundly altered our understanding of the regulation of eukaryotic gene expression. Although the identification of ncRNAs has become a standard experimental approach, the functional characterization of these diverse ncRNAs remains a major challenge. In this chapter, we highlight recent progress in the methods to identify lncRNAs and the techniques to study the molecular function of these lncRNAs and the application of these techniques to the study of plant lncRNAs.
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http://dx.doi.org/10.1007/978-1-4939-9045-0_1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684206PMC
August 2019

Long Noncoding RNAs in Plants.

Adv Exp Med Biol 2017 ;1008:133-154

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO, 64110, USA.

The eukaryotic genomes are pervasively transcribed. In addition to protein-coding RNAs, thousands of long noncoding RNAs (lncRNAs) modulate key molecular and biological processes. Most lncRNAs are found in the nucleus and associate with chromatin, but lncRNAs can function in both nuclear and cytoplasmic compartments. Emerging work has found that many lncRNAs regulate gene expression and can affect genome stability and nuclear domain organization both in plant and in the animal kingdom. Here, we describe the major plant lncRNAs and how they act, with a focus on research in Arabidopsis thaliana and our emerging understanding of lncRNA functions in serving as molecular sponges and decoys, functioning in regulation of transcription and silencing, particularly in RNA-directed DNA methylation, and in epigenetic regulation of flowering time.
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http://dx.doi.org/10.1007/978-981-10-5203-3_5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689229PMC
January 2018

Small RNAs: essential regulators of gene expression and defenses against environmental stresses in plants.

Wiley Interdiscip Rev RNA 2016 05 28;7(3):356-81. Epub 2016 Feb 28.

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO, USA.

Eukaryotic genomes produce thousands of diverse small RNAs (smRNAs), which play vital roles in regulating gene expression in all conditions, including in survival of biotic and abiotic environmental stresses. SmRNA pathways intersect with most of the pathways regulating different steps in the life of a messenger RNA (mRNA), starting from transcription and ending at mRNA decay. SmRNAs function in both nuclear and cytoplasmic compartments; the regulation of mRNA stability and translation in the cytoplasm and the epigenetic regulation of gene expression in the nucleus are the main and best-known modes of smRNA action. However, recent evidence from animal systems indicates that smRNAs and RNA interference (RNAi) also participate in the regulation of alternative pre-mRNA splicing, one of the most crucial steps in the fast, efficient global reprogramming of gene expression required for survival under stress. Emerging evidence from bioinformatics studies indicates that a specific class of plant smRNAs, induced by various abiotic stresses, the sutr-siRNAs, has the potential to target regulatory regions within introns and thus may act in the regulation of splicing in response to stresses. This review summarizes the major types of plant smRNAs in the context of their mechanisms of action and also provides examples of their involvement in regulation of gene expression in response to environmental cues and developmental stresses. In addition, we describe current advances in our understanding of how smRNAs function in the regulation of pre-mRNA splicing. WIREs RNA 2016, 7:356-381. doi: 10.1002/wrna.1340 For further resources related to this article, please visit the WIREs website.
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http://dx.doi.org/10.1002/wrna.1340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671677PMC
May 2016

Stress-induced endogenous siRNAs targeting regulatory intron sequences in Brachypodium.

RNA 2015 Feb 5;21(2):145-63. Epub 2014 Dec 5.

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA

Exposure to abiotic stresses triggers global changes in the expression of thousands of eukaryotic genes at the transcriptional and post-transcriptional levels. Small RNA (smRNA) pathways and splicing both function as crucial mechanisms regulating stress-responsive gene expression. However, examples of smRNAs regulating gene expression remain largely limited to effects on mRNA stability, translation, and epigenetic regulation. Also, our understanding of the networks controlling plant gene expression in response to environmental changes, and examples of these regulatory pathways intersecting, remains limited. Here, to investigate the role of smRNAs in stress responses we examined smRNA transcriptomes of Brachypodium distachyon plants subjected to various abiotic stresses. We found that exposure to different abiotic stresses specifically induced a group of novel, endogenous small interfering RNAs (stress-induced, UTR-derived siRNAs, or sutr-siRNAs) that originate from the 3' UTRs of a subset of coding genes. Our bioinformatics analyses predicted that sutr-siRNAs have potential regulatory functions and that over 90% of sutr-siRNAs target intronic regions of many mRNAs in trans. Importantly, a subgroup of these sutr-siRNAs target the important intron regulatory regions, such as branch point sequences, that could affect splicing. Our study indicates that in Brachypodium, sutr-siRNAs may affect splicing by masking or changing accessibility of specific cis-elements through base-pairing interactions to mediate gene expression in response to stresses. We hypothesize that this mode of regulation of gene expression may also serve as a general mechanism for regulation of gene expression in plants and potentially in other eukaryotes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338343PMC
http://dx.doi.org/10.1261/rna.047662.114DOI Listing
February 2015

The role of the Arabidopsis Exosome in siRNA-independent silencing of heterochromatic loci.

PLoS Genet 2013 Mar 28;9(3):e1003411. Epub 2013 Mar 28.

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.

The exosome functions throughout eukaryotic RNA metabolism and has a prominent role in gene silencing in yeast. In Arabidopsis, exosome regulates expression of a "hidden" transcriptome layer from centromeric, pericentromeric, and other heterochromatic loci that are also controlled by small (sm)RNA-based de novo DNA methylation (RdDM). However, the relationship between exosome and smRNAs in gene silencing in Arabidopsis remains unexplored. To investigate whether exosome interacts with RdDM, we profiled Arabidopsis smRNAs by deep sequencing in exosome and RdDM mutants and also analyzed RdDM-controlled loci. We found that exosome loss had a very minor effect on global smRNA populations, suggesting that, in contrast to fission yeast, in Arabidopsis the exosome does not control the spurious entry of RNAs into smRNA pathways. Exosome defects resulted in decreased histone H3K9 dimethylation at RdDM-controlled loci, without affecting smRNAs or DNA methylation. Exosome also exhibits a strong genetic interaction with RNA Pol V, but not Pol IV, and physically associates with transcripts produced from the scaffold RNAs generating region. We also show that two Arabidopsis rrp6 homologues act in gene silencing. Our data suggest that Arabidopsis exosome may act in parallel with RdDM in gene silencing, by epigenetic effects on chromatin structure, not through siRNAs or DNA methylation.
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http://dx.doi.org/10.1371/journal.pgen.1003411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610620PMC
March 2013
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