Genome-wide characterization of human L1 antisense promoter-driven transcripts

Area of Science:

• Genomics
• Molecular Biology
• Human Genetics

Background:

• Long INterspersed Element-1 (LINE-1 or L1) is the only active transposable element in the human genome.
• Human-specific L1 subfamilies are competent for retrotransposition.
• L1 promoters are bidirectional, with sense and antisense orientations.

Purpose of the Study:

• To investigate the impact of L1 antisense promoter activity on cellular transcriptomes.
• To identify and characterize chimeric transcripts originating from the L1 antisense promoter.

Main Methods:

• Analysis of GenBank ESTs for L1 antisense promoter-initiated transcripts.
• Identification of chimeric transcripts using long-read RNA-seq.
• Validation of selected transcripts using RT-PCR and Sanger sequencing.

Main Results:

• Identified 988 putative L1 antisense chimeric transcripts, with 911 previously unreported.
• These transcripts are alternative genic transcripts, sense-oriented relative to the host gene.
• L1 antisense promoters show enrichment for YY1 transcription factor and active promoter histone modifications.

Conclusions:

• Comprehensive characterization of human L1 antisense promoter-driven transcripts.
• Evidence supports transcription in various human cell types.
• Antisense transcripts impact up to 4% of human genes, revealing a new facet of L1 biology.