Genes & Genomics

, Volume 38, Issue 1, pp 69–79 | Cite as

Analysis of L1-chimeric transcripts derived from bidirectional promoter of human-specific L1

Research Article

Abstract

LINE-1s (L1s) have contributed to gene structure variation and they can affect the expression of nearby genes in the human genome. Here, we collected 35 human-specific L1s that may play a role as alternative promoters. In addition, we identified 54 L1-chimeric transcripts generated from these L1s using bioinformatics’ tools and carried out reverse transcription-PCR to analyze their expressional pattern in 20 human normal tissues and 9 human cancer tissues. Consequently, 30 L1-chimeric transcripts were experimentally confirmed. Most L1-chimeric transcripts were broadly expressed. Interestingly, we found that EST CD709363 derived from C14orf37 gene was expressed in trachea only among normal tissues, but it was expressed in several cancer tissues including brain, lung, skin, and esophagus. We also newly identified three alternative transcripts, which were not in the UCSC genome database. One alternative transcript was derived from RABGAP1L gene and the other two transcripts were from CAMK4 gene. In addition, we analyzed putative transcription binding sites within the four L1s located in the promoter region. These had several transcription factor binding sites related to promoters. Our results show that human-specific L1s could contribute to human transcriptome diversity and transcriptional gene expression in different types of human tissues.

Keywords

Alternative splicing Human-specific LINE-1 (L1) L1-chimeric transcript Promoter 

Supplementary material

13258_2015_363_MOESM1_ESM.pptx (43 kb)
Structural scheme of human-specific L1s (A) L1 had inserted into the human genome after the divergence of human and chimpanzee lineages and generated human-specific alternative transcripts by providing new promoters. (B) A full-length L1 contains untranslated regions (UTRs) at both side of two open reading frames (ORFs) and is about 6.9 kb in length. The 5′UTR of L1 provides bidirectional promoters, which can result in L1-chimeric transcripts (PPTX 42 kb).
13258_2015_363_MOESM2_ESM.pptx (92 kb)
Sequencing analysis of L1-chimeric transcripts L1-chimeric transcripts (A) BE567753 and (B) DA456960 from sense L1s and (C) AV691164 and (D) CD709363 from antisense L1s were validated by sequencing analysis. We aligned and compared annotated sequences (upper) with analyzed sequences in this study (bottom). Gray box indicates L1 sequences (PPTX 92 kb).
13258_2015_363_MOESM3_ESM.xlsx (14 kb)
Supplementary material 3 (XLSX 13 kb)
13258_2015_363_MOESM4_ESM.xlsx (15 kb)
Supplementary material 4 (XLSX 14 kb)

References

  1. Aerbajinai W, Giattina M, Lee YT, Raffeld M, Miller JL (2003) The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation. Blood 102:712–717CrossRefPubMedGoogle Scholar
  2. Babushok DV, Kazazian HH Jr (2007) Progress in understanding the biology of the human mutagen LINE-1. Hum Mutat 28:527–539CrossRefPubMedGoogle Scholar
  3. Boissinot S, Entezam A, Young L, Munson PJ, Furano AV (2004) The insertional history of an active family of L1 retrotransposons in humans. Genome Res 14:1221–1231CrossRefPubMedPubMedCentralGoogle Scholar
  4. Caceres JF, Kornblihtt AR (2002) Alternative splicing: multiple control mechanisms and involvement in human disease. Trends Genet 18:186–193CrossRefPubMedGoogle Scholar
  5. Cordaux R, Batzer MA (2009) The impact of retrotransposons on human genome evolution. Nat Rev Genet 10:691–703CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656CrossRefPubMedGoogle Scholar
  7. Cruickshanks HA, Tufarelli C (2009) Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter. Genomics 94:397–406CrossRefPubMedGoogle Scholar
  8. Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658CrossRefPubMedGoogle Scholar
  9. Delsert C, Morin N, Klessig DF (1989) cis-acting elements and a trans-acting factor affecting alternative splicing of adenovirus L1 transcripts. Mol Cell Biol 9:4364–4371CrossRefPubMedPubMedCentralGoogle Scholar
  10. Farooq M, Kim Y, Im S, Chung E, Hwang S, Sohn M, Kim M, Kim J (2001) Cloning of BNIP3 h, a member of proapoptotic BNIP3 family genes. Exp Mol Med 33:169–173CrossRefPubMedGoogle Scholar
  11. Feng Q, Moran JV, Kazazian HH Jr, Boeke JD (1996) Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87:905–916CrossRefPubMedGoogle Scholar
  12. Gao T, Furnari F, Newton AC (2005) PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 18:13–24CrossRefPubMedGoogle Scholar
  13. Graveley BR (2001) Alternative splicing: increasing diversity in the proteomic world. Trends Genet 17:100–107CrossRefPubMedGoogle Scholar
  14. Kim DS, Hahn Y (2011) Identification of human-specific transcript variants induced by DNA insertions in the human genome. Bioinformatics 27:14–21CrossRefPubMedGoogle Scholar
  15. Landry JR, Mager DL, Wilhelm BT (2003) Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet 19:640–648CrossRefPubMedGoogle Scholar
  16. Lee D, Sykes SM, Kalaitzidis D, Lane AA, Kfoury Y, Raaijmakers MH, Wang YH, Armstrong SA, Scadden DT (2014) Transmembrane inhibitor of RICTOR/mTORC2 in hematopoietic progenitors. Stem Cell Reports 3:832–840CrossRefPubMedPubMedCentralGoogle Scholar
  17. Luan DD, Korman MH, Jakubczak JL, Eickbush TH (1993) Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72:595–605CrossRefPubMedGoogle Scholar
  18. Matlik K, Redik K, Speek M (2006) L1 antisense promoter drives tissue-specific transcription of human genes. J Biomed Biotechnol 2006:71753CrossRefPubMedPubMedCentralGoogle Scholar
  19. Nigumann P, Redik K, Matlik K, Speek M (2002) Many human genes are transcribed from the antisense promoter of L1 retrotransposon. Genomics 79:628–634CrossRefPubMedGoogle Scholar
  20. Smit AF (1999) Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev 9(6):657–663CrossRefPubMedGoogle Scholar
  21. Speek M (2001) Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes. Mol Cell Biol 21:1973–1985CrossRefPubMedPubMedCentralGoogle Scholar
  22. Swergold GD (1990) Identification, characterization, and cell specificity of a human LINE-1 promoter. Mol Cell Biol 10:6718–6729CrossRefPubMedPubMedCentralGoogle Scholar
  23. Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C et al (2005) A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics 4:1920–1932CrossRefPubMedGoogle Scholar
  24. Warnefors M, Pereira V, Eyre-Walker A (2010) Transposable elements: insertion pattern and impact on gene expression evolution in hominids. Mol Biol Evol 27:1955–1962CrossRefPubMedGoogle Scholar
  25. Wilson AS, Power BE, Molloy PL (2007) DNA hypomethylation and human diseases. Biochim Biophys Acta 1775:138–162PubMedGoogle Scholar
  26. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss JW 3rd et al (2009) BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130CrossRefPubMedPubMedCentralGoogle Scholar
  27. Yasuda M, Han JW, Dionne CA, Boyd JM, Chinnadurai G (1999) BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3. Cancer Res 59:533–537PubMedGoogle Scholar
  28. Zhou J, Yu X, Wang J, Li T, Jin T, Lei D, Pan X (2015) Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma. PLoS One 10:e0119405CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer-Science and Media 2015

Authors and Affiliations

  1. 1.Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative MedicineDankook UniversityCheonanRepublic of Korea

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