Transcription Regulation Depends on Release from Chromatin

By LabMedica International staff writers
Posted on 09 May 2018

A team of German genome researchers has demonstrated that release from chromatin is a crucial functional aspect of long noncoding RNAs in transcription regulation of their target genes.

Long non-coding RNAs (lncRNAs) are considered to be non-protein coding transcripts longer than 200 nucleotides. This somewhat arbitrary limit distinguishes lncRNAs from small regulatory RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. LncRNAs have been found to be involved in numerous biological roles including imprinting, epigenetic gene regulation, cell cycle and apoptosis, and metastasis and prognosis in solid tumors. Most lncRNAs are expressed only in a few cells rather than whole tissues, or they are expressed at very low levels, making them difficult to study. Their name notwithstanding, long non-coding RNAs (lncRNAs) have been found to actually encode synthesis of small polypeptides that can fine-tune the activity of critical cellular components. LncRNAs are often enriched in the nucleus and at chromatin, but whether their dissociation from chromatin is important for their role in transcription regulation is unclear.

Image: The long non-coding RNA called A-ROD is only functional the moment it is released from chromatin into the nucleoplasm. At this transient phase, it can bring transcription factors to specific sites in DNA to enhance gene expression. After its complete release from chromatin, A-ROD is no longer active (Photo courtesy of Evgenia Ntini, Max Planck Institute for Molecular Genetics).

To better understand the link between lncRNAs and chromatin, investigators at the Max Planck Institute for Molecular Genetics (Berlin, Germany) grouped lncRNAs using epigenetic marks, expression, and strength of chromosomal interactions.

They reported in the April 24, 2018, online edition of the journal Nature Communications that lncRNAs transcribed from loci engaged in strong long-range chromosomal interactions were less abundant at chromatin, suggesting the release from chromatin was a crucial functional aspect of lncRNAs in transcription regulation of their target genes.

To gain mechanistic insight into this mechanism, they functionally validated the lncRNA A-ROD, which enhances DKK1 (Dickkopf-related protein 1) transcription via its nascent spliced released form. Detailed validation provided evidence that the regulatory effect was exerted by A-ROD at its release from the chromatin-associated site of transcription.

These findings provide evidence that the regulatory interaction required dissociation of A-ROD from chromatin, with target specificity having been established during the period of chromosomal proximity.

Related Links:
Max Planck Institute for Molecular Genetics