scholarly journals H4K20me3 marks distal intergenic and repetitive regions in human mature spermatozoa

Development ◽  
2021 ◽  
Author(s):  
Nihan Ozturk ◽  
Temuujin Dansranjavin ◽  
Sabrina Gies ◽  
Damien Calay ◽  
Shanjid Shiplu ◽  
...  
Keyword(s):  
K562 Cells ◽  
Gene Clusters ◽  
Human Sperm ◽  
Cell Types ◽  
Low Complexity ◽  
Wide Distribution ◽  
Developmental Factors ◽  
Genes Encoding ◽  
Intergenic Regions ◽  
Transcription Activators

Sperm histones (SHs) represent an essential part of the paternally transmitted epigenome, but uncertainty exists about the role of those remaining in non-coding and repetitive DNA. We therefore analyzed the genome-wide distribution of the heterochromatic marker H4K20me3 in human sperm and somatic (K562) cells. To specify the function of SHs, we compared all H4K20me3-containing and -free loci in sperm genome. Sperm and somatic cells possessed a very similar H4K20me3-distribution: H4K20me3 peaks occurred mostly in distal intergenic regions and repetitive gene clusters (in particular genes encoding odorant binding factors and zinc-finger antiviral proteins). In both cell types, H4K20me3 peaks were enriched in LINEs, ERVs, satellite DNA and low complexity repeats. In contrast, H4K20me3-free nucleosomes occurred more frequently in genic regions (in particular promoters, exons, 5’-UTR and 3’-UTR) and were enriched in genes encoding developmental factors (in particular transcription activators and repressors). H4K20me3-free nucleosomes were also detected in substantial quantities in distal intergenic regions and were enriched in SINEs. Thus, evidence suggests that paternally transmitted histones may have a dual purpose: maintenance and regulation of heterochromatin and guidance towards transcription of euchromatin.

scholarly journals Two Similar Gene Clusters Coding for Enzymes of a New Type of Aerobic 2-Aminobenzoate (Anthranilate) Metabolism in the BacteriumAzoarcus evansii

2001 ◽  
Vol 183 (18) ◽  
pp. 5268-5278 ◽  
Author(s):  
Karola Schühle ◽  
Martina Jahn ◽  
Sandro Ghisla ◽  
Georg Fuchs
Keyword(s):  
Gene Clusters ◽  
Old Yellow Enzyme ◽  
Coding Regions ◽  
System A ◽  
Coa Ligase ◽  
Genes Encoding ◽  
Intergenic Regions ◽  
New Type ◽  
Coa Thioesters ◽  
Substrate Binding Protein

ABSTRACT In the β-proteobacterium Azoarcus evansii, the aerobic metabolism of 2-aminobenzoate (anthranilate), phenylacetate, and benzoate proceeds via three unprecedented pathways. The pathways have in common that all three substrates are initially activated to coenzyme A (CoA) thioesters and further processed in this form. The two initial steps of 2-aminobenzoate metabolism are catalyzed by a 2-aminobenzoate-CoA ligase forming 2-aminobenzoyl-CoA and by a 2-aminobenzoyl-CoA monooxygenase/reductase (ACMR) forming 2-amino-5-oxo-cyclohex-1-ene-1-carbonyl-CoA. Eight genes possibly involved in this pathway, including the genes encoding 2-aminobenzoate-CoA ligase and ACMR, were detected, cloned, and sequenced. The sequence of the ACMR gene showed that this enzyme is an 87-kDa fusion protein of two flavoproteins, a monooxygenase (similar to salicylate monooxygenase) and a reductase (similar to old yellow enzyme). Besides the genes for the initial two enzymes, genes for three enzymes of a β-oxidation pathway were found. A substrate binding protein of an ABC transport system, a MarR-like regulator, and a putative translation inhibitor protein were also encoded by the gene cluster. The data suggest that, after monooxygenation/reduction of 2-aminobenzoyl-CoA, the nonaromatic CoA thioester intermediate is metabolized further by β-oxidation. This implies that all subsequent intermediates are CoA thioesters and that the alicyclic carbon ring is not cleaved oxygenolytically. Surprisingly, the cluster of eight genes, which form an operon, is duplicated. The two copies differ only marginally within the coding regions but differ substantially in the respective intergenic regions. Both copies of the genes are coordinately expressed in cells grown aerobically on 2-aminobenzoate.

scholarly journals Evidence of the Involvement of a Cyclase Gene in the Biosynthesis of Ochratoxin A in Aspergillus carbonarius

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 892
Author(s):  
Massimo Ferrara ◽  
Antonia Gallo ◽  
Carla Cervini ◽  
Lucia Gambacorta ◽  
Michele Solfrizzo ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Biosynthetic Pathway ◽  
Gene Clusters ◽  
Wide Distribution ◽  
Ring Closure ◽  
Fungal Genome ◽  
Great Utility ◽  
Genes Encoding ◽  
Food And Feed ◽  
First Time

Ochratoxin A (OTA) is a well-known mycotoxin with wide distribution in food and feed. Fungal genome sequencing has great utility for identifying secondary metabolites gene clusters for known and novel compounds. A comparative analysis of the OTA-biosynthetic cluster in A. steynii, A. westerdijkiae, A. niger, A. carbonarius, and P. nordicum has revealed a high synteny in OTA cluster organization in five structural genes (otaA, otaB, ota, otaR1, and otaD). Moreover, a recent detailed comparative genome analysis of Aspergilli OTA producers led to the identification of a cyclase gene, otaY, located in the OTA cluster between the otaA and otaB genes, encoding for a predicted protein with high similarity to SnoaLs domain. These proteins have been shown to catalyze ring closure steps in the biosynthesis of polyketide antibiotics produced in Streptomyces. In the present study, we demonstrated an upregulation of the cyclase gene in A. carbonarius under OTA permissive conditions, consistent with the expression trends of the other OTA cluster genes and their role in OTA biosynthesis by complete gene deletion. Our results pointed out the involvement of a cyclase gene in OTA biosynthetic pathway for the first time. They represent a step forward in the understanding of the molecular basis of OTA biosynthesis in A. carbonarius.

scholarly journals Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 298
Author(s):  
Despoina Konstantinou ◽  
Rafael V. Popin ◽  
David P. Fewer ◽  
Kaarina Sivonen ◽  
Spyros Gkelis
Keyword(s):  
Natural Products ◽  
Microbial Communities ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Marine Sponges ◽  
Genome Reduction ◽  
Extracellular Polysaccharides ◽  
Comparative Genomic ◽  
Symbiotic Relationships ◽  
Genes Encoding

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

Long-Living Budding Yeast Cell Subpopulation Induced by Ethanol/Acetate and Respiration

2019 ◽  
Vol 75 (8) ◽  
pp. 1448-1456 ◽  
Author(s):  
Young-Yon Kwon ◽  
Seung-Soo Kim ◽  
Han-Jun Lee ◽  
Seo-Hyeong Sheen ◽  
Kyoung Heon Kim ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Budding Yeast ◽  
Gradient Centrifugation ◽  
Carbon Sources ◽  
Cell Types ◽  
Glucose Sensing ◽  
Differentially Expressed ◽  
Cell Subpopulation ◽  
Genes Encoding ◽  
Cell Transcriptome

Abstract Budding yeast generate heterogeneous cells that can be separated into two distinctive cell types: short-living low-density and long-living high-density (HD) cells by density gradient centrifugation. We found that ethanol and acetate induce formation of HD cells, and mitochondrial respiration is required. From their transcriptomes and metabolomes, we found upregulated differentially expressed genes in HD cells involved in the RGT2/RGT1 glucose sensing pathway and its downstream genes encoding hexose transporters. For HD cells, we determined an abundance of various carbon sources including glucose, lactate, pyruvate, trehalose, mannitol, mannose, and galactose. Other upregulated differentially expressed genes in HD cells were involved in the TORC1–SCH9 signaling pathway and its downstream genes involved in cytoplasmic translation. We also measured an abundance of free amino acids in HD cells including valine, proline, isoleucine, and glutamine. These characteristics of the HD cell transcriptome and metabolome may be important conditions for maintaining a long-living phenotype.

scholarly journals Molecular hallmarks of heterochronic parabiosis at single cell resolution

2020 ◽  
Author(s):  
Róbert Pálovics ◽  
Andreas Keller ◽  
Nicholas Schaum ◽  
Weilun Tan ◽  
Tobias Fehlmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Disease Risk ◽  
Global Gene Expression ◽  
Cell Types ◽  
The Body ◽  
Hematopoietic Stem ◽  
Gene Sets ◽  
Genes Encoding ◽  
Systemic Understanding

Slowing or reversing biological ageing would have major implications for mitigating disease risk and maintaining vitality. While an increasing number of interventions show promise for rejuvenation, the effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. We performed single-cell RNA-sequencing on 13 organs to reveal cell type specific responses to young or aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, hematopoietic stem cells, hepatocytes, and endothelial cells from multiple tissues appear especially responsive. On the pathway level, young blood invokes novel gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. Intriguingly, we observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it. Altogether, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

scholarly journals Expression of transcription factors (STAT 2, 3, 4, and 6, HDAC1, HDAC2) in craniopharyngioma

2021 ◽  
pp. 12
Keyword(s):  
Cyst Formation ◽  
Cell Types ◽  
Surrounding Tissue ◽  
Cytokine Signaling ◽  
High Recurrence Rate ◽  
Brain Invasion ◽  
Macrophage Response ◽  
Enhanced Expression ◽  
Critical Components ◽  
Transcription Activators

Background: Craniopharyngioma is a benign tumor of the sellar region that is typically characterized by a maldevelopment tumor with a high recurrence rate, as well as substantial morbidity and mortality in the long term. Signal transducers and transcription activators have been identified as critical components of cytokine signaling pathways that have previously been documented in craniopharyngioma-related literature. Purpose: The primary goal of this investigation is to examine transcription factor expression in craniopharyngiomas. In addition, a clinical-pathological and immunohistochemistry correlation will be sought. The current study enlisted the participation of forty patients. AdaCPs exhibited: β-catenin STAT2, STAT3, STAT6, and HDAC1 expression. While, STAT4, HDAC2, and GATA 3 were all negative. TTF1 was found in proteinaceous substances within the cyst formation (OMF). β-FGR, DPGR, TNFa, and Nrf2 were found to be associated with inflammation, OMF presence, and finger protrusion in brain surrounding tissue or brain invasion. Conclusions: Tumor recurrence was associated with increased expression of STAT3, STAT6, HDAC, β-catenin, and TNFα in WLA when compared to no recurrence. Coexpression of β-catenin, STAT2, STAT3, and STAT6 with TNFα was also shown using double fluorescence merge stains. There was no association between HDAC1 and HDAC2 coexpression and β-catenin, notably in the WLAs. Discussion: Histologically complicated features include cystic and solid components, the latter of which is made up of diverse morphological cell types. HDAC1 and HDAC2 regulate the enhanced expression of inflammatory genes during inflammation and macrophage response.

scholarly journals Thyroid hormone regulated genes in cerebral cortex development

2017 ◽  
Vol 232 (2) ◽  
pp. R83-R97 ◽  
Author(s):  
Juan Bernal
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormones ◽  
Fetal Development ◽  
Cell Types ◽  
Control Of Gene Expression ◽  
Cellular Targets ◽  
Cerebral Cortex Development ◽  
Subplate Neurons ◽  
Genes Encoding

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T3 with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T3 during specific stages of development is required. In our laboratory, we previously identified genes regulated by T3 in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T3 can be identified. In addition, many of the genes regulated transcriptionally by T3 have defined roles in cortex development, from which the role of T3 can be derived. This review analyzes the specific roles of T3-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T3 during the second trimester of fetal development. The main cellular targets of T3 appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T3 regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

Abstract O.16: Comprehensive Genotyping Of The FCGR2/3 Locus Reveals A Novel Association Of FCGR2C-ORF With Susceptibility To Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Taco W Kuijpers ◽  
Carline E Tacke ◽  
Sietse Q Nagelkerke ◽  
Willemijn B Breunis ◽  
Long T Hoang ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Myeloid Cell ◽  
Cell Types ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Homologous Genes ◽  
Genes Encoding ◽  
Novel Association ◽  
Family Based

The human FCGR2/3 locus contains highly homologous genes encoding the five major receptors for IgG (Fc-gamma receptors, FcγRs). In two prior GWAS on Kawasaki disease (KD), a SNP in FCGR2A (131H>R; rs1801274) was identified to be associated with disease susceptibility. However, the FCGR2/3 locus contains multiple single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), which were not covered by the detection platforms used in the GWAS. In this study we therefore focused on further fine-mapping of this locus to investigate the association of the different genetic variations with KD susceptibility. A highly accurate and validated multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze all functionally relevant SNPs and CNVs within this locus. In a genetic association study involving case-control and family-based testing with 1028 patients with KD, the previous finding of FCGR2A-131H as a susceptibility marker for KD was confirmed (OR 1.16; 95%CI 1.08-1.32, meta-P = 0.01). In addition, we found a novel significant association of the FCGR2C-ORF haplotype with susceptibility to KD (OR 1.34; 95% confidence interval 1.11-1.62, meta-P = 0.003). FCGR2C-ORF leads to the expression of an extra, functionally activating FcγR (i.e. FcγRIIc) on myeloid cell types and NK cells. Being absent in Asian individuals, the FCGR2C-ORF haplotype only contributed to KD susceptibility in European subjects, independent of the established association with FCGR2A-H131R. We did not find any significant association of CNV of the locus with susceptibility to KD. Our data point to an important role of the activating FcγRs in KD pathology. We hypothesize that the identified functional SNPs might alter the balance between the activating and inhibitory FcγRs leading to unbalanced inflammation and KD.

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