Genome-wide characterization of human L1 antisense promoter-driven transcripts. BMC Genomics 2016 Jun 14;17:463
Date
06/16/2016Pubmed ID
27301971Pubmed Central ID
PMC4908685DOI
10.1186/s12864-016-2800-5Scopus ID
2-s2.0-84974795127 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
BACKGROUND: Long INterspersed Element-1 (LINE-1 or L1) is the only autonomously active, transposable element in the human genome. L1 sequences comprise approximately 17 % of the human genome, but only the evolutionarily recent, human-specific subfamily is retrotransposition competent. The L1 promoter has a bidirectional orientation containing a sense promoter that drives the transcription of two proteins required for retrotransposition and an antisense promoter. The L1 antisense promoter can drive transcription of chimeric transcripts: 5' L1 antisense sequences spliced to the exons of neighboring genes.
RESULTS: The impact of L1 antisense promoter activity on cellular transcriptomes is poorly understood. To investigate this, we analyzed GenBank ESTs for messenger RNAs that initiate in the L1 antisense promoter. We identified 988 putative L1 antisense chimeric transcripts, 911 of which have not been previously reported. These appear to be alternative genic transcripts, sense-oriented with respect to gene and initiating near, but typically downstream of, the gene transcriptional start site. In multiple cell lines, L1 antisense promoters display enrichment for YY1 transcription factor and histone modifications associated with active promoters. Global run-on sequencing data support the activity of the L1 antisense promoter. We independently detected 124 L1 antisense chimeric transcripts using long read Pacific Biosciences RNA-seq data. Furthermore, we validated four chimeric transcripts by quantitative RT-PCR and Sanger sequencing and demonstrated that they are readily detectable in many normal human tissues.
CONCLUSIONS: We present a comprehensive characterization of human L1 antisense promoter-driven transcripts and provide substantial evidence that they are transcribed in a variety of human cell-types. Our findings reveal a new wide-reaching aspect of L1 biology by identifying antisense transcripts affecting as many as 4 % of all human genes.
Author List
Criscione SW, Theodosakis N, Micevic G, Cornish TC, Burns KH, Neretti N, Rodić NAuthor
Toby Charles Cornish MD, PhD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsExpressed Sequence Tags
Genome, Human
Genome-Wide Association Study
Humans
Long Interspersed Nucleotide Elements
Mice
Promoter Regions, Genetic
RNA, Antisense
Retroelements
Transcription, Genetic
