Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements.

Area of Science:

• Genomics
• Molecular Biology
• Developmental Biology

Background:

• Ultraconserved elements (UCEs) are highly conserved mammalian genomic regions with incompletely understood functions.
• Previous research indicated some UCEs function as enhancers or are transcribed in human tissues.
• Concomitant enhancer and transcription functions were previously observed in only one UCE and isolated non-ultraconserved elements.

Purpose of the Study:

• To investigate the transcriptional activity of UCEs during mouse development.
• To determine if UCEs possess both enhancer and transcriptional functions concurrently.
• To characterize the nature of UCE transcripts.

Main Methods:

• Custom microarray analysis of UCE transcription during mouse development.
• Integration of published microarray and next-generation sequencing (NGS) datasets.
• Polymerase chain reaction (PCR) validation experiments.
• Meta-analysis of RNA-Seq datasets.

Main Results:

• A significant proportion of non-exonic UCEs are transcribed from a single DNA strand across all developmental stages studied.
• UCE transcripts are unlikely to be short RNAs; some may encode nuclear transcripts.
• The transcriptional function of non-exonic UCEs frequently overlaps with their known enhancer function during mouse development.
• Expression levels in non-exonic UCEs are significantly higher than in random genomic regions and comparable to known enhancers.

Conclusions:

• The concurrent enhancer and transcript functions in non-exonic UCEs are more prevalent than previously recognized.
• Non-exonic UCEs likely encode long RNAs transcribed from a single DNA strand.
• These findings contribute to understanding the functional roles of UCEs in mammalian genomes.