Search Our Scientific Publications & Authors

Cell 2021 Mar 30. Epub 2021 Mar 30.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Read More

Cancer Cell 2021 Mar 30. Epub 2021 Mar 30.

The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. Electronic address:

Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. Read More

Nucleic Acids Res 2021 Apr 9. Epub 2021 Apr 9.

Université de Strasbourg, CNRS UMR7104, INSERM U1258, IGBMC, F-67400 Illkirch, France.

Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Read More

Nucleic Acids Res 2021 Apr 9. Epub 2021 Apr 9.

Institute of Gene Biology Russian Academy of Science, 119334 Moscow, Russia.

Liquid-liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within the cell nucleus. However, the role played by LLPS in chromatin folding in living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) and Hi-C techniques, we studied the effects of 1,6-hexanediol (1,6-HD)-mediated LLPS disruption/modulation on higher-order chromatin organization in living cells. Read More

Nucleic Acids Res 2021 Apr 9. Epub 2021 Apr 9.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, 430070 Wuhan, China.

Lysine acetylation (Kac) is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. Read More

J Cell Biol 2021 Jun;220(6)

Waksman Institute and Department of Genetics, Rutgers, the State University of New Jersey, Piscataway, NJ.

The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosome passenger complex (CPC), which consists of INCENP, Borealin, Survivin, and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. Read More

J Zhejiang Univ Sci B 2021 Apr;22(4):253-284

Department of Biology, East Carolina University, Greenville, NC 27858, USA.

Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010s, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) has rapidly been developed into a robust, multifunctional genome editing tool with many uses. Following the discovery of the initial CRISPR/Cas-based system, the technology has been advanced to facilitate a multitude of different functions. These include development as a base editor, prime editor, epigenetic editor, and CRISPR interference (CRISPRi) and CRISPR activator (CRISPRa) gene regulators. Read More

Essays Biochem 2021 Apr 9. Epub 2021 Apr 9.

Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine (CMB), Friedrich Schiller University Jena, Hans-Knöll-Str. 2, Jena 07745, Germany.

The genomes of complex eukaryotes largely contain non-protein-coding DNA, which is pervasively transcribed into a plethora of non-coding RNAs (ncRNAs). The functional importance of many of these ncRNAs has been investigated in the last two decades, revealing their crucial and multifaceted roles in chromatin regulation. A common mode of action of ncRNAs is the recruitment of chromatin modifiers to specific regions in the genome. Read More

Reproduction 2021 Apr 1. Epub 2021 Apr 1.

C Lin, Centre for Reproductive Health, The University of Edinburgh MRC Centre for Reproductive Health, Edinburgh, United Kingdom of Great Britain and Northern Ireland.

Elucidating the mechanisms underpinning fertilisation is essential to optimising IVF procedures. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. Read More

Elife 2021 Apr 9;10. Epub 2021 Apr 9.

Allen Institute for Immunology, Seattle, United States.

Single-cell measurements of cellular characteristics have been instrumental in understanding the heterogeneous pathways that drive differentiation, cellular responses to signals, and human disease. Recent advances have allowed paired capture of protein abundance and transcriptomic state, but a lack of epigenetic information in these assays has left a missing link to gene regulation. Using the heterogeneous mixture of cells in human peripheral blood as a test case, we developed a novel scATAC-seq workflow that increases signal-to-noise and allows paired measurement of cell surface markers and chromatin accessibility: integrated cellular indexing of chromatin landscape and epitopes, called ICICLE-seq. Read More

Front Cell Dev Biol 2021 23;9:633305. Epub 2021 Mar 23.

Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, Australia.

DNA repair and metabolic pathways are vital to maintain cellular homeostasis in normal human cells. Both of these pathways, however, undergo extensive changes during tumorigenesis, including modifications that promote rapid growth, genetic heterogeneity, and survival. While these two areas of research have remained relatively distinct, there is growing evidence that the pathways are interdependent and intrinsically linked. Read More

Evid Based Complement Alternat Med 2021 26;2021:5570356. Epub 2021 Mar 26.

Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Read More

J Oncol 2021 25;2021:5512524. Epub 2021 Mar 25.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Read More

Front Cell Neurosci 2021 23;15:633668. Epub 2021 Mar 23.

ALS Therapy Development Institute, Cambridge, MA, United States.

Hexanucleotide repeat expansion (G4C2) mutations in the gene C9ORF72 account for approximately 30% of familial cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well as approximately 7% of sporadic cases of ALS. G4C2 mutations are known to result in the production of five species of dipeptide repeat proteins (DRPs) through non-canonical translation processes. Arginine-enriched dipeptide repeat proteins, glycine-arginine (polyGR), and proline-arginine (polyPR) have been demonstrated to be cytotoxic and deleterious in multiple experimental systems. Read More

Nat Cell Biol 2021 Apr 8;23(4):391-400. Epub 2021 Apr 8.

Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna Biocenter (VBC), Vienna, Austria.

Mobile transposable elements (TEs) not only participate in genome evolution but also threaten genome integrity. In healthy cells, TEs that encode all of the components that are necessary for their mobility are specifically silenced, yet the precise mechanism remains unknown. Here, we characterize the mechanism used by a conserved class of chromatin remodelers that prevent TE mobility. Read More

Genome Res 2021 Apr 8. Epub 2021 Apr 8.

VIB-KU Leuven Center for Brain & Disease Research, KU Leuven;

Genomic sequence variation within enhancers and promoters can have a significant impact on the cellular state and phenotype. However, sifting through the millions of candidate variants in a personal genome or a cancer genome, to identify those that impact -regulatory function, remains a major challenge. Interpretation of noncoding genome variation benefits from explainable artificial intelligence to predict and interpret the impact of a mutation on gene regulation. Read More

Genome Res 2021 Apr 8. Epub 2021 Apr 8.

University of California, Los Angeles;

Steps of mRNA maturation are important gene regulatory events that occur in distinct cellular locations. However, transcriptomic analyses often lose information on the subcellular distribution of processed and unprocessed transcripts. We generated extensive RNA-seq datasets to track mRNA maturation across subcellular locations in mouse embryonic stem cells, neuronal progenitor cells, and postmitotic neurons. Read More

J Insect Physiol 2021 Apr 5:104236. Epub 2021 Apr 5.

Department of Biology, Ecology and Earth Science, University of Calabria, Italy. Electronic address:

Herbicides have become the most commonly applied agrochemicals in agroecosystems. Thus, basic knowledge of their physiological effects on insects is needed, especially for understanding their impact on beneficial insect species. In this study, we evaluated the effect of a pendimethalin-based herbicide (PND) on the cellular immune response of the carabid beetle Harpalus (Pseudoophonus) rufipes (De Geer 1774) (Coleoptera, Carabidae), acting as biocontrol agent in agroecosystems. Read More

Life Sci 2021 Apr 5:119398. Epub 2021 Apr 5.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. Read More

Plant Cell 2019 Sep;31(9):2259-2275

Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, 1030 Vienna, Austria.

Ribosomal RNA genes are arranged in large arrays with hundreds of rDNA units in tandem. These highly repetitive DNA elements pose a risk to genome stability since they can undergo nonallelic exchanges. During meiosis, DNA double-strand breaks (DSBs) are induced as part of the regular program to generate gametes. Read More

Plant Cell 2019 Sep;31(9):2035-2051

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

Centromeres mediate the pairing of homologous chromosomes during meiosis; this pairing is particularly challenging for polyploid plants such as hexaploid bread wheat (Triticum aestivum), as their meiotic machinery must differentiate homologs from similar homoeologs. However, the sequence compositions (especially functional centromeric satellites) and evolutionary history of wheat centromeres are largely unknown. Here, we mapped T. Read More

Hum Mol Genet 2021 Apr 7. Epub 2021 Apr 7.

Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT USA.

Several studies have reported association between leukocyte telomere length (LTL) and neuropsychiatric disorders. While telomere length is affected by environmental factors, genetic variants in certain loci are strongly associated with LTL. Thus, we aimed to identify the genomic relationship between genetic variants of LTL with brain-based regulatory changes and brain volume. Read More

Plant Cell 2019 Nov;31(11):2573-2595

Center for Plant Cell Biology and Botany and Plant Sciences Department, University of California, Riverside, California 92521.

Gene regulation is a dynamic process involving changes ranging from the remodeling of chromatin to preferential translation. To understand integrated nuclear and cytoplasmic gene regulatory dynamics, we performed a survey spanning the epigenome to translatome of Arabidopsis (Arabidopsis thaliana) seedlings in response to hypoxia and reoxygenation. This included chromatin assays (examining histones, accessibility, RNA polymerase II [RNAPII], and transcription factor binding) and three RNA assays (nuclear, polyadenylated, and ribosome-associated). Read More

Andrology 2021 Apr 8. Epub 2021 Apr 8.

Centre for Reproductive Medicine and Andrology, University of Münster, Münster, Germany.

Background: Sperm DNA integrity has become one of the most discussed and promising biomarkers for the assessment of male fertility. However, an easy-to-apply method capable of estimating DNA fragmentation in the live fraction of spermatozoa has remained elusive, preventing this parameter from being fully applied in clinical settings.

Objectives: To validate a novel co-staining for the analysis of DNA fragmentation in membrane-intact spermatozoa. Read More

Bioessays 2021 Apr 8:e2000335. Epub 2021 Apr 8.

MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.

Post-transcriptional regulation faces a distinctive challenge in gametes. Transcription is limited when the germ cells enter the division phase due to condensed chromatin, while gene expression during gamete maturation, fertilization, and early cleavage depends on existing mRNA post-transcriptional coordination. The dynamics of the 3'-poly(A) tail play crucial roles in defining mRNA fate. Read More

Bioinformatics 2021 Apr 8. Epub 2021 Apr 8.

Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Hannoversche Str. 28, 10115 Berlin, Germany.

Motivation: Genome Architecture Mapping (GAM) was recently introduced as a digestion- and ligation-free method to detect chromatin conformation. Orthogonal to existing approaches based on chromatin conformation capture (3C), GAM's ability to capture both inter- and intra-chromosomal contacts from low amounts of input data makes it particularly well suited for allele-specific analyses in a clinical setting. Allele-specific analyses are powerful tools to investigate the effects of genetic variants on many cellular phenotypes including chromatin conformation, but require the haplotypes of the individuals under study to be known a-priori. Read More

Endocr Connect 2021 Apr 1. Epub 2021 Apr 1.

O Mäkitie, University of Helsinki, Helsinki, Finland.

In the last decade, the widespread use of massively-parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized. Read More

Reprod Domest Anim 2021 Apr 8. Epub 2021 Apr 8.

Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Instituto de Investigación y Tecnología en Reproducción Animal (INITRA), Cátedra de Teriogenología, Buenos Aires, Argentina.

Semen cryopreservation is not available for massive use in South American Camelids (SACs) due to the lack of an efficient protocol and the low pregnancy rates obtained with artificial insemination (AI). The use of a single cryoprotectant (CP) is commonly used in SACs frozen semen. The objective of the study was to evaluate the combined cryoprotective capacity of two permeable CPs at different stages of the cryopreservation protocol in llama semen. Read More

Eur Rev Med Pharmacol Sci 2021 Mar;25(6):2528-2541

Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Objective: Several studies have demonstrated that long non-coding RNA can act as crucial roles during the progression of various tumors, including prostate cancer (PCa). We aimed to determine lncRNA LINC01194(LINC01194) expression in prostate cancer (PCa) and examine its influence on tumor behaviors of PCa cells.

Patients And Methods: RT-PCR was performed to examine LINC01194 and PAX5's expression levels in PCa tissues and cell lines. Read More

Front Med (Lausanne) 2021 22;8:614829. Epub 2021 Mar 22.

Laboratory of Molecular Nephrology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. Read More