scholarly journals Heterogeneity in the Epigenetic Landscape of Murine Testis-Specific Histone Variants TH2A and TH2B Sharing the Same Bi-Directional Promoter

2021 ◽  
Vol 9 ◽  
Author(s):  
Isha Singh ◽  
Priyanka Parte
Keyword(s):  
Dna Sequences ◽  
Histone Variants ◽  
Open Chromatin ◽  
Epigenetic Landscape ◽  
Double Knockout ◽  
Significant Term ◽  
Functional Relevance ◽  
Genomic Regions ◽  
Nucleosome Disassembly ◽  
Mitochondrial Chromosome

Testis-specific histone variants are crucial to promote open chromatin structure to enable nucleosome disassembly in the final stages of spermiogenesis. However, even after histone replacement, mature sperm retain a proportion of these variants, the function of which is unknown. The present study aimed to understand the functional relevance of the retained H2B and H2A variants, TH2B and TH2A. While no literature is available on the phenotype of TH2A knockouts, TH2B/TH2A double knockout male mice are reported to be infertile. In this study, ChIP-seq analysis was done for TH2B and TH2A to understand the epigenomics of the retained TH2B and TH2A, using murine caudal sperm. Distribution across genomic partitions revealed ∼35% of the TH2B peaks within ±5 kb of TSS whereas TH2A peaks distribution was sparse at TSS. Gene Ontology revealed embryo development as the most significant term associated with TH2B. Also, based on genomic regions, TH2B was observed to be associated with spindle assembly and various meiosis-specific genes, which is an important finding as TH2A/TH2B DKO mice have been reported to have defective cohesin release. A comparison of mouse and human TH2B-linked chromatin revealed 26% overlap between murine and human TH2B-associated genes. This overlap included genes crucial for embryogenesis. Most importantly, heterogeneity in the epigenetic landscape of TH2A and TH2B was seen, which is intriguing as TH2B and TH2A are well reported to be present in the same nucleosomes to promote open chromatin. Additionally, unlike TH2B, TH2A was enriched on the mitochondrial chromosome. TH2A was found to be associated with Nuclear insertion of Mitochondrial DNA sequences (NUMTs) in sperm. A comprehensive analysis of these observations indicates novel functions for the sperm-retained TH2B and TH2A.

Genome-wide profiling of histone 3 lysine 36 trimethylation in clear cell renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 464-464
Author(s):  
Thai Huu Ho ◽  
Jeong-Heon Lee ◽  
Rafael Nunez Nateras ◽  
Erik P. Castle ◽  
Melissa L. Stanton ◽  
...  
Keyword(s):  
Cell Lines ◽  
Dna Sequences ◽  
Open Chromatin ◽  
Sequencing Analysis ◽  
Gene Desert ◽  
Cell Renal Cell Carcinoma ◽  
Chip Sequencing ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

464 Background: Although the von Hippel-Lindau (VHL) tumor suppressor gene is mutated in 60% of ccRCC, deletion of VHL in mice is insufficient for tumorigenesis. Sequencing of ccRCC tumors identified mutations in SETD2, a histone H3 lysine 36 (H3K36) trimethyltransferase. We hypothesize that loss of SETD2 methyltransferase activity alters the genome wide pattern of H3K36 trimethylation (H3K36me3) in ccRCC, and contributes to the cancer phenotype. Methods: To generate a genome-wide profile of H3K36me3 in frozen nephrectomy samples and RCC cell lines, we optimized a chromatin immunoprecipitation (ChIP) protocol for the isolation of DNA associated with H3K36me3. H3K36me3 is associated with open chromatin and an H3K36me3-specific antibody was used for immunoprecipitation of endogenous H3K36me3-bound DNA. ChIP PCR primers were optimized for active genes, such as actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a “gene desert” on chromosome 12 (negative control). ChIP libraries were then generated from 3 paired uninvolved kidney and RCC and 2 RCC cell lines. In order to identify H3K36Me3 upregulated regions in uninvolved kidney and RCC, reads from the ChIP sequencing were mapped to the human genome using Burrows-Wheeler Aligner and SICER algorithms. Results: Using ChIP PCR, we found that active genomic regions were enriched 15-30 fold over the negative controls indicating that the quality and yield of immunoprecipitated DNA/chromatin complexes from frozen tissue was sufficient for ChIP sequencing. A preliminary ChIP sequencing analysis of RCC cell lines and frozen ccRCC tissue indicates that H3K36me3 enriched DNA sequences were mapped to exons (31.3%) compared to introns (13.5%, p<0.001), consistent with the role of H3K36me3 in transcription. Conclusions: Genomic regions enriched for H3K36Me3 binding were identified from patient-derived tissue and RCC cell lines. Current efforts are focused on comparing the H3K36me3 profiles between matched tumor and uninvolved kidney ChIP libraries to generate a genome wide map of dysregulated H3K36me3 modifications.

scholarly journals Constitutive expression, not a particular primary sequence, is the important feature of the H3 replacement variant hv2 in Tetrahymena thermophila.

1997 ◽  
Vol 17 (11) ◽  
pp. 6303-6310 ◽  
Author(s):  
L Yu ◽  
M A Gorovsky
Keyword(s):  
Protein Sequence ◽  
Tetrahymena Thermophila ◽  
Histone H3 ◽  
Constitutive Expression ◽  
Histone Variants ◽  
Wild Type ◽  
Ciliated Protozoan ◽  
Knockout Mutant ◽  
Double Knockout ◽  
Constitutive Synthesis

Although quantitatively minor replication-independent (replacement) histone variants have been found in a wide variety of organisms, their functions remain unknown. Like the H3.3 replacement variants of vertebrates, hv2, an H3 variant in the ciliated protozoan Tetrahymena thermophila, is synthesized and deposited in nuclei of nongrowing cells. Although hv2 is clearly an H3.3-like replacement variant by its expression, sequence analysis indicates that it evolved independently of the H3.3 variants of multicellular eukaryotes. This suggested that it is the constitutive synthesis, not the particular protein sequence, of these variants that is important in the function of H3 replacement variants. Here, we demonstrate that the gene (HHT3) encoding hv2 or either gene (HHT1 or HHT2) encoding the abundant major H3 can be completely knocked out in Tetrahymena. Surprisingly, when cells lacking hv2 are starved, a major histone H3 mRNA transcribed by the HHT2 gene, which is synthesized little, if at all, in wild-type nongrowing cells, is easily detectable. Both HHT2 and HHT3 knockout strains show no obvious defect during vegetative growth. In addition, a mutant with the double knockout of HHT1 and HHT3 is viable while the HHT2 HHT3 double-knockout mutant is not. These results argue strongly that cells require a constitutively expressed H3 gene but that the particular sequence being expressed is not critical.

scholarly journals Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations

2018 ◽  
Author(s):  
Kiran Lalwani ◽  
Shivani Sheth ◽  
Inayatullah Sheikh ◽  
Afzal Ansari ◽  
Fulesh Kunwar ◽  
...  
Keyword(s):  
Dna Sequences ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Fusion Gene ◽  
Genetic Material ◽  
Chromosomal Translocations ◽  
In Silico Study ◽  
Clinical Consequences ◽  
The Stability ◽  
Genomic Regions

Chromosomal translocations involve exchange of genetic material between non- homologous chromosomes leading to the formation of a fusion gene with altered function. The clinical consequences of non-random and recurrent chromosomal translocations have been so well understood in carcinogenesis that they serve as diagnostic and prognostic markers and also help in therapy decisions, mainly in leukemia and lymphoma. However, the molecular mechanisms underlying these recurrent genetic exchanges are yet to be understood. Various approaches employed include the extent of the vicinity of the partner chromosomes in the nucleus, DNA sequences at the breakpoints, etc. The present study addresses the stability of DNA sequences at the breakpoint regions using in-silico approach in terms of physicochemical properties such as; AT%, flexibility, melting temperature, enthalpy, entropy, stacking energy and free energy. Changes in these properties may lead to instability of DNA which could affect gene expression in particular and genome organization in general. Our study indicates that the fusion sequences are comparatively more unstable and hence, more prone to breakage. Current study along with others could lead to developing a model for predicting breakage prone genomic regions using this novel in-silico approach.

scholarly journals Reference Genome Assembly for Australian Ascochyta rabiei Isolate ArME14

2020 ◽  
Vol 10 (7) ◽  
pp. 2131-2140
Author(s):  
Ramisah Mohd Shah ◽  
Angela H. Williams ◽  
James K. Hane ◽  
Julie A. Lawrence ◽  
Lina M. Farfan-Caceres ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Dna Sequences ◽  
Genome Assembly ◽  
Ascochyta Blight ◽  
Ascochyta Rabiei ◽  
Causal Organism ◽  
Protein Coding ◽  
Putative Protein ◽  
Genomic Regions ◽  
Genome Assemblies

Ascochyta rabiei is the causal organism of ascochyta blight of chickpea and is present in chickpea crops worldwide. Here we report the release of a high-quality PacBio genome assembly for the Australian A. rabiei isolate ArME14. We compare the ArME14 genome assembly with an Illumina assembly for Indian A. rabiei isolate, ArD2. The ArME14 assembly has gapless sequences for nine chromosomes with telomere sequences at both ends and 13 large contig sequences that extend to one telomere. The total length of the ArME14 assembly was 40,927,385 bp, which was 6.26 Mb longer than the ArD2 assembly. Division of the genome by OcculterCut into GC-balanced and AT-dominant segments reveals 21% of the genome contains gene-sparse, AT-rich isochores. Transposable elements and repetitive DNA sequences in the ArME14 assembly made up 15% of the genome. A total of 11,257 protein-coding genes were predicted compared with 10,596 for ArD2. Many of the predicted genes missing from the ArD2 assembly were in genomic regions adjacent to AT-rich sequence. We compared the complement of predicted transcription factors and secreted proteins for the two A. rabiei genome assemblies and found that the isolates contain almost the same set of proteins. The small number of differences could represent real differences in the gene complement between isolates or possibly result from the different sequencing methods used. Prediction pipelines were applied for carbohydrate-active enzymes, secondary metabolite clusters and putative protein effectors. We predict that ArME14 contains between 450 and 650 CAZymes, 39 putative protein effectors and 26 secondary metabolite clusters.

scholarly journals A genomic perspective on the taxonomy of the subtribe Carcharodina (Lepidoptera: Hesperiidae: Carcharodini)

Zootaxa ◽  
2020 ◽  
Vol 4748 (1) ◽  
pp. 182-194 ◽  
Author(s):  
JING ZHANG ◽  
ERNST BROCKMANN ◽  
QIAN CONG ◽  
JINHUI SHEN ◽  
NICK V. GRISHIN
Keyword(s):  
Dna Sequences ◽  
Type Species ◽  
Phylogenetic Trees ◽  
Type Specimens ◽  
African Species ◽  
Protein Coding ◽  
Coding Regions ◽  
As Species ◽  
Close Relatives ◽  
Genomic Regions

We obtained whole genome shotgun sequences and phylogenetically analyzed protein-coding regions of representative skipper butterflies from the genus Carcharodus Hübner, [1819] and its close relatives. Type species of all available genus-group names were sequenced. We find that species attributed to four exclusively Old World genera (Spialia Swinhoe, 1912, Gomalia Moore, 1879, Carcharodus Hübner, [1819] and Muschampia Tutt, 1906) form a monophyletic group that we call a subtribe Carcharodina Verity, 1940. In the phylogenetic trees built from various genomic regions, these species form 7 (not 4) groups that we treat as genera. We find that Muschampia Tutt, 1906 is not monophyletic, and the 5th group is formed by currently monotypic genus Favria Tutt, 1906 new status (type species Hesperia cribrellum Eversmann, 1841), which is sister to Gomalia. The 6th and 7th groups are composed of mostly African species presently placed in Spialia. These groups do not have names and are described here as Ernsta Grishin, gen. n. (type species Pyrgus colotes Druce, 1875) and Agyllia Grishin, gen. n. (type species Pyrgus agylla Trimen, 1889). Two subgroups are recognized in Ernsta: the nominal subgenus and a new one: Delaga Grishin, subgen. n. (type species Pyrgus delagoae Trimen, 1898). Next, we observe that Carcharodus is not monophyletic, and species formerly placed in subgenera Reverdinus Ragusa, 1919 and Lavatheria Verity, 1940 are here transferred to Muschampia. Furthermore, due to differences in male genitalia or DNA sequences, we reinstate Gomalia albofasciata Moore, 1879 and Gomalia jeanneli (Picard, 1949) as species, not subspecies or synonyms of Gomalia elma (Trimen, 1862), and Spialia bifida (Higgins, 1924) as a species, not subspecies of Spialia zebra (Butler, 1888). Sequencing of the type specimens reveals 2.2-3.2% difference in COI barcodes, the evidence that combined with wing pattern differences suggests a new status of a species for Spialia lugens (Staudinger, 1886) and Spialia carnea (Reverdin, 1927), formerly subspecies of Spialia orbifer (Hübner, [1823]). 

scholarly journals Open chromatin structure in PolyQ disease-related genes: a potential mechanism for CAG repeat expansion in the normal human population

2019 ◽  
Vol 1 (1) ◽  
pp. e3-e3 ◽  
Author(s):  
Matan Sorek ◽  
Lea R Z Cohen ◽  
Eran Meshorer
Keyword(s):  
Cag Repeat ◽  
Open Chromatin ◽  
Epigenetic Landscape ◽  
Active Chromatin ◽  
Pluripotent Cells ◽  
Polyq Disease ◽  
Cag Repeat Expansion ◽  
Normal Human ◽  
Disease Related Genes ◽  
Disease Associated Genes

Abstract The human genome contains dozens of genes that encode for proteins containing long poly-glutamine repeats (polyQ, usually encoded by CAG codons) of 10Qs or more. However, only nine of these genes have been reported to expand beyond the healthy variation and cause diseases. To address whether these nine disease-associated genes are unique in any way, we compared genetic and epigenetic features relative to other types of genes, especially repeat containing genes that do not cause diseases. Our analyses show that in pluripotent cells, the nine polyQ disease-related genes are characterized by an open chromatin profile, enriched for active chromatin marks and depleted for suppressive chromatin marks. By contrast, genes that encode for polyQ-containing proteins that are not associated with diseases, and other repeat containing genes, possess a suppressive chromatin environment. We propose that the active epigenetic landscape support decreased genomic stability and higher susceptibility for expansion mutations.

scholarly journals Chromatin Decondensation and Nuclear Reprogramming by Nucleoplasmin

2006 ◽  
Vol 26 (4) ◽  
pp. 1259-1271 ◽  
Author(s):  
Hiroshi Tamada ◽  
Nguyen Van Thuan ◽  
Peter Reed ◽  
Dominic Nelson ◽  
Nobuko Katoku-Kikyo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Kinase Inhibitor ◽  
Histone H3 ◽  
Histone Variants ◽  
Epigenetic Modifications ◽  
Sperm Chromatin ◽  
Open Chromatin ◽  
Chromatin Decondensation ◽  
H3 Phosphorylation ◽  
H3 Acetylation

ABSTRACT Somatic cell nuclear cloning has repeatedly demonstrated striking reversibility of epigenetic regulation of cell differentiation. Upon injection into eggs, the donor nuclei exhibit global chromatin decondensation, which might contribute to reprogramming the nuclei by derepressing dormant genes. Decondensation of sperm chromatin in eggs is explained by the replacement of sperm-specific histone variants with egg-type histones by the egg protein nucleoplasmin (Npm). However, little is known about the mechanisms of chromatin decondensation in somatic nuclei that do not contain condensation-specific histone variants. Here we found that Npm could widely decondense chromatin in undifferentiated mouse cells without overt histone exchanges but with specific epigenetic modifications that are relevant to open chromatin structure. These modifications included nucleus-wide multiple histone H3 phosphorylation, acetylation of Lys 14 in histone H3, and release of heterochromatin proteins HP1β and TIF1β from the nuclei. The protein kinase inhibitor staurosporine inhibited chromatin decondensation and these epigenetic modifications with the exception of H3 acetylation, potentially linking these chromatin events. At the functional level, Npm pretreatment of mouse nuclei facilitated activation of four oocyte-specific genes from the nuclei injected into Xenopus laevis oocytes. Future molecular elucidation of chromatin decondensation by Npm will significantly contribute to our understanding of the plasticity of cell differentiation.

scholarly journals Gene Expression in Trypanosomatid Parasites

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Santiago Martínez-Calvillo ◽  
Juan C. Vizuet-de-Rueda ◽  
Luis E. Florencio-Martínez ◽  
Rebeca G. Manning-Cela ◽  
Elisa E. Figueroa-Angulo
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Histone Variants ◽  
Protein Coding ◽  
Functional Studies ◽  
Polycistronic Transcription ◽  
General Transcription Factors ◽  
Genome Wide ◽  
Trypanosomatid Parasites

The parasitesLeishmaniaspp.,Trypanosoma brucei,andTrypanosoma cruziare the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids.In silicoanalyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

scholarly journals The dominant hepatitis B virus genotype identified in Tibet is a C/D hybrid

2002 ◽  
Vol 83 (11) ◽  
pp. 2773-2777 ◽  
Author(s):  
Chaoyin Cui ◽  
Jinxiu Shi ◽  
Lijian Hui ◽  
Huifeng Xi ◽  
Zhuoma ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Sequences ◽  
The Other ◽  
Virus Genotype ◽  
Hbv Genotypes ◽  
B Virus ◽  
Genotype C ◽  
Genomic Regions ◽  
Positive Population

There are no reports on DNA sequences of hepatitis B virus (HBV) strains from Tibet, although this highland area has a high HBsAg-positive population. We characterized HBV isolates from sera of 26 HBsAg-positive Tibetans. To determine the HBV genotypes and their phylogenetic relationships, we sequenced two genomic regions, one including the pre-S1/pre-S2/S region and the other including the pre-C/C region. The sequences were classified into two different genotypes based on different regions of the genome, except for one isolate. To clarify this finding, two complete HBV genomes that represented the two groups of isolates were sequenced. From the sequencing results, we concluded that HBV strains in Tibet may be classified as genotype C, and there are at least two subgroups. The dominant subgroup is a C/D hybrid with serotype ayw2, and the other is genotype C with serotype adw. This is the first report of complete nucleotide sequences of HBV from Tibet. These results contribute to the investigation of recombinant HBV strains throughout the world and should encourage further study of genotypes and recombination in HBV from this particular region.

scholarly journals Sites of active gene regulation in the prenatal frontal cortex and their role in neuropsychiatric disorders

2021 ◽  
Author(s):  
Manuela R. Kouakou ◽  
Darren Cameron ◽  
Eilis Hannon ◽  
Emma L. Dempster ◽  
Jonathan Mill ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Major Depressive Disorder ◽  
Genetic Variation ◽  
Frontal Cortex ◽  
Fetal Brain ◽  
Neuropsychiatric Disorders ◽  
Open Chromatin ◽  
Major Depressive ◽  
Genomic Regions ◽  
Neuropsychiatric Conditions

Common genetic variation appears to largely influence risk for neuropsychiatric disorders through effects on gene regulation. It is therefore possible to shed light on the biology of these conditions by testing for enrichment of associated genetic variation within regulatory genomic regions operating in specific tissues or cell types. Here, we have used ATAC-Seq to map open chromatin (an index of active regulatory genomic regions) in bulk tissue, NeuN+ and NeuN- nuclei from the prenatal human frontal cortex, and tested enrichment of SNP heritability for 5 neuropsychiatric disorders (autism spectrum disorder, ADHD, bipolar disorder, major depressive disorder and schizophrenia) within these regions. We observed significant enrichment of SNP heritability for ADHD, major depressive disorder and schizophrenia within open chromatin regions mapped in bulk fetal frontal cortex, and for all 5 tested neuropsychiatric conditions when we restricted these sites to those overlapping histone modifications indicative of enhancers (H3K4me1) or promoters (H3K4me3) in fetal brain. SNP heritability for neuropsychiatric disorders was significantly enriched in open chromatin regions identified in fetal frontal cortex NeuN- as well as NeuN+ nuclei overlapping fetal brain H3K4me1 or H3K4me3 sites. We additionally demonstrate the utility of our mapped open chromatin regions for prioritizing potentially functional SNPs at genome-wide significant risk loci for neuropsychiatric disorders. Our data provide evidence for an early neurodevelopmental component to a range of neuropsychiatric conditions and highlight an important role for regulatory genomic regions active within both NeuN+ and NeuN- cells of the prenatal brain.

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