Disease relevance of Long Interspersed Nucleotide Elements

• We have identified an RNA-dependent DNA polymerase activity in the microsomal fraction of human pluri-potential embryonal carcinoma cells NTera2D1, which are known to express the full length coding strand of the genomic Line-1 (L1) elements [1].
• Mammalian LINE-1 (L1) elements belong to the superfamily of autonomously replicating retrotransposable elements that lack the long terminal repeated (LTR) sequences typical of retroviruses and retroviral-like retrotransposons [2].

High impact information on Long Interspersed Nucleotide Elements

• We previously isolated two human L1 elements (L1.2 and LRE2) as the progenitors of disease-producing insertions [3].
• The breakpoint occurs at 9q34 within COL5A1 intron 24 and interestingly, within a LINE-1 (L1) element at Xp21 [4].
• Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion [5].
• This novel mutation of the dystrophin gene has important implications regarding retrotransposition of an active L1 element and provides a new insight into the origins of mutations in the dystrophin gene [6].
• In addition, LINE 1 elements, satellite 2 sequences, and CpG island-containing DNA were identified [7].

Biological context of Long Interspersed Nucleotide Elements

• The X chromosome is enriched 2-fold for L1 repetitive elements, with the greatest enrichment observed for a restricted subset of LINE-1 elements that were active <100 million years ago [8].
• Like the HIS3 pseudogenes whose formation depends on Ty1 RT, the HIS3 pseudogenes generated by L1 RT are joined to Ty1 sequences and often are part of complex arrays of Ty1 elements, multiple HIS3 pseudogenes, and hybrid Ty1/L1 elements [9].
• Because the unmethylated state of the ICF inactive X L1s probably reflects their methylation status at the time of X inactivation, these data suggest that unmethylated L1 elements, but not methylated L1s, may have a role in the spreading of X chromosome inactivation [10].
• Retrotransposable element-1 (RTE-1) is a class of long interspersed nucleotide elements that contain in its open reading frame an apurinic/apyrimidinic endonuclease domain (AP-END) and a reverse transcriptase domain [11].
• Initial evidence suggested that the only actively transposing L1 elements in the modern mouse genome were a young subfamily of A-type elements [12].

Anatomical context of Long Interspersed Nucleotide Elements

• Rearrangement of a VH-associated LINE-1 element with the expressed IgH cluster in a murine myeloma cell line [13].
• Previously, we developed a cultured cell assay that uses a neomycin phosphotransferase ( neo ) retrotransposition cassette to determine relative retrotransposition frequencies among various L1 elements [14].

Associations of Long Interspersed Nucleotide Elements with chemical compounds

• The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family [15].
• A LINE-1 element insertion in the 5'-noncoding region of caprine growth hormone receptor gene [16].
• We report a method for studying global DNA methylation based on using bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such as Alu elements and long interspersed nucleotide elements (LINE) [17].

Gene context of Long Interspersed Nucleotide Elements

• The spa mutation is an insertion of a LINE-1 element in the gene for the beta subunit of the glycine receptor, Glrb [18].
• An L1 element disrupts human bone sialoprotein promoter: lack of tissue-specific regulation by distalless5 (Dlx5) and runt homeodomain protein2 (Runx2)/core binding factor a1 (Cbfa1) elements [19].
• Selection is for the restoration of URA3 gene activity attendant on recombination into an L1 element in the YAC insert [20].
• A LINE-1 element lies at 5 kb upstream of CYBB in normal persons, and the 5' breakpoint of the deletion in the patient is in the LINE-1 element [21].
• The truncated L1 element was inserted into CYP51P2 approximately 6 MYR ago [15].

References