Simple repetitive sequences and gene expression

2000 ◽  
Vol 34 (3) ◽  
pp. 303-307 ◽  
Author(s):  
A. V. Pisarchik ◽  
N. A. Kartel’
2021 ◽  
Author(s):  
Kevin M. Creamer ◽  
Eric C. Larsen ◽  
Jeanne B. Lawrence

Repetitive sequences including transposable elements (TEs) and transposon-derived fragments account for nearly half of the human genome. While transposition-competent TEs must be repressed to maintain genomic stability, mutated and fragmented TEs comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here we analyzed published ChIP-seq data sets to identify proteins broadly enriched on TEs in the human genome. We show two of the proteins identified, C2H2 zinc finger-containing proteins ZNF146 (also known as OZF) and ZNF507, are targeted to distinct sites within LINE-1 ORF2 at thousands of locations in the genome. ZNF146 binding sites are found at old and young LINE-1 elements. In contrast, ZNF507 preferentially binds at young LINE-1 sequences correlated to sequence changes in LINE-1 elements at ZNF507s binding site. To gain further insight into ZNF146 and ZNF507 function, we disrupt their expression in HEK293 cells using CRISPR/Cas9 and perform RNA sequencing, finding modest gene expression changes in cells where ZNF507 has been disrupted. We further identify a physical interaction between ZNF507 and PRMT5, suggesting ZNF507 may target arginine methylation activity to LINE-1 sequences.


Author(s):  
Ning Ji ◽  
Lifang Yan ◽  
Zhixue Song ◽  
Shufeng Liu ◽  
Chao Liu ◽  
...  

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Tariq Ezaz ◽  
Janine E. Deakin

Sex chromosomes are the most dynamic entity in any genome having unique morphology, gene content, and evolution. They have evolved multiple times and independently throughout vertebrate evolution. One of the major genomic changes that pertain to sex chromosomes involves the amplification of common repeats. It is hypothesized that such amplification of repeats facilitates the suppression of recombination, leading to the evolution of heteromorphic sex chromosomes through genetic degradation of Y or W chromosomes. Although contrasting evidence is available, it is clear that amplification of simple repetitive sequences played a major role in the evolution of Y and W chromosomes in vertebrates. In this review, we present a brief overview of the repetitive DNA classes that accumulated during sex chromosome evolution, mainly focusing on vertebrates, and discuss their possible role and potential function in this process.


1992 ◽  
Vol 12 (9) ◽  
pp. 3807-3818 ◽  
Author(s):  
R E Johnson ◽  
S T Henderson ◽  
T D Petes ◽  
S Prakash ◽  
M Bankmann ◽  
...  

rad5 (rev2) mutants of Saccharomyces cerevisiae are sensitive to UV light and other DNA-damaging agents, and RAD5 is in the RAD6 epistasis group of DNA repair genes. To unambiguously define the function of RAD5, we have cloned the RAD5 gene, determined the effects of the rad5 deletion mutation on DNA repair, DNA damage-induced mutagenesis, and other cellular processes, and analyzed the sequence of RAD5-encoded protein. Our genetic studies indicate that RAD5 functions primarily with RAD18 in error-free postreplication repair. We also show that RAD5 affects the rate of instability of poly(GT) repeat sequences. Genomic poly(GT) sequences normally change length at a rate of about 10(-4); this rate is approximately 10-fold lower in the rad5 deletion mutant than in the corresponding isogenic wild-type strain. RAD5 encodes a protein of 1,169 amino acids of M(r) 134,000, and it contains several interesting sequence motifs. All seven conserved domains found associated with DNA helicases are present in RAD5. RAD5 also contains a cysteine-rich sequence motif that resembles the corresponding sequences found in 11 other proteins, including those encoded by the DNA repair gene RAD18 and the RAG1 gene required for immunoglobin gene arrangement. A leucine zipper motif preceded by a basic region is also present in RAD5. The cysteine-rich region may coordinate the binding of zinc; this region and the basic segment might constitute distinct DNA-binding domains in RAD5. Possible roles of RAD5 putative ATPase/DNA helicase activity in DNA repair and in the maintenance of wild-type rates of instability of simple repetitive sequences are discussed.


Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 227-238 ◽  
Author(s):  
William G Kelly ◽  
SiQun Xu ◽  
Mary K Montgomery ◽  
Andrew Fire

In screening for embryonic-lethal mutations in Caernorhabditis elegans, we defined an essential gene (let-858) that encodes a nuclear protein rich in acidic and basic residues. We have named this product nucampholin. Closely homologous sequences in yeast, plants, and mammals demonstrate strong evolutionary conservation in eukaryotes. Nucampholin resides in all nuclei of C. elegans and is essential in early development and in differentiating tissue. Antisense-mediated depletion of LET-858 activity in early embryos causes a lethal phenotype similar to characterized treatments blocking embryonic gene expression. Using transgene-rescue, we demonstrated the additional requirement for let-858 in the larval germline. The broad requirements allowed investigation of soma-germline differences in gene expression. When introduced into standard transgene arrays, let-858 (like many other C. elegans genes) functions well in soma but poorly in germline. We observed incremental silencing of simple let-858 arrays in thefirstfew generations following transformation and hypothesized that silencing might reflect recognition of arrays as repetitive or heterochromatin-like. To give the transgene a more physiological context, we included an excess of random genomic fragments with the injected DNA. The resulting transgenes show robust expression in both germline and soma. Our results suggest the possibility of concerted mechanisms for silencing unwanted germline expression of repetitive sequences.


Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mahboubeh R. Rostami ◽  
Martina Bradic

Abstract Background Transposable elements (TEs) are repetitive sequences of viral origin that compose almost half of the human genome. These elements are tightly controlled within cells, and if activated, they can cause changes in both gene regulation and immune viral responses that have been associated with several chronic inflammatory diseases in humans. As oxidants are potent activators of TEs, and because oxidative injury is a major risk factor in relation to idiopathic pulmonary fibrosis (IPF), we hypothesized that TEs might be involved in the regulation of gene expression and so contribute to inflammation in cases of IPF. IPF is a fatal lung disease that involves the gradual replacement of the alveolar tissue with fibrotic scars as well as the accumulation of inflammatory cells in the lower respiratory tract. Although IPF is known to occur as a result of the complex interaction between age, environmental risk factors (i.e., oxidative stress) and genetics, the relative contributions of these factors to the disease remain unclear. To determine whether TEs are associated with IPF, we compared the transcriptional profiles of the genes and TEs of lung cells obtained from both healthy donors and IPF patients. Results We quantified TE and gene expression levels using a published bulk RNA-seq dataset containing 24 subjects (16 donors and eight IPF patients), including three lung-cell types per subject, as well as an scRNA-seq dataset concerning 16 subjects (eight donors and eight IPF patients). We found evidence of TE dysregulation in the alveolar type II lung cells and alveolar macrophages of the IPF patients. In addition, the activation of the LINE1 family of elements in IPF is associated with the increased expression of TE cellular regulators (MOV10, IFI16, SAMHD1, and APOBECG3), interferon-stimulating genes (ISG15, IFI6, IFI27, IFI44, and OAS1), chemokines (CX3CL1 and CXCL9), and interleukins (IL15RA). We also propose that TE derepression might be involved in the regulation of previously reported IPF candidate genes (MUC5B, CHL1, SPP1, and MMP7). Conclusion Based on our findings, we propose that TE derepression plays an important role in the regulation of gene expression and can also prompt both the recruitment of inflammatory processes and the disruption of the immunological balance, which can lead to chronic inflammation in IPF.


Genome ◽  
1992 ◽  
Vol 35 (3) ◽  
pp. 436-442 ◽  
Author(s):  
Kurt Weising ◽  
Dieter Kaemmer ◽  
Franz Weigand ◽  
Jörg T. Epplen ◽  
Gunter Kahl

Synthetic oligonucleotides complementary to simple repetitive DNA sequences were used to detect inter- and intra-specific polymorphisms in a leguminous crop plant (chickpea, Cicer arietinum) and its wild relatives. All the investigated repetitive motifs [(GACA)4, (GATA)4, (GTG)5, (CA)8, (TCC)5, (GGAT)4, and (AGTTT)4] were abundantly present and polymorphic in the chickpea genome. Different probes revealed different levels of variability. Whereas species-specific banding patterns were obtained with the (GTG)5 probe, other probes revealed differences between accessions, or even individuals. The somatic multilocus patterns were stable for all probes.Key words: genetic polymorphism, simple repetitive sequences, DNA fingerprinting, synthetic oligonucleotide probes.


1995 ◽  
Vol 16 (1) ◽  
pp. 1705-1714 ◽  
Author(s):  
Samir K. Brahmachari ◽  
Gopinath Meera ◽  
Partha S. Sarkar ◽  
Pichumani Balagurumoorthy ◽  
Jalaj Tripathi ◽  
...  

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