page_title: Telomeric repeat–containing RNA
section_title: Heterochromatin Regulation
hierarchical_section_title: Telomeric repeat–containing RNA / Functions of TERRA / Heterochromatin Regulation
caption_attribution_description: English: The heterochromatic state of chromatin effects relative TERRA expression. In general, closed chromatin structure leads to low level TERRA expression, while relaxed chromatin structure allows for higher levels of TERRA expression due to increased transcription. Heterochromatic state can be modified by factors such as the NuA Histone Acetyltransferase Complex, BAF-Type SWI/SNF Nucleosome Remodeling Complex, and the NoRC Chromatin Remodeling Complex
context_page_description: Telomeric repeat-containing RNA is a long non-coding RNA transcribed from telomeres - repetitive nucleotide regions found on the ends of chromosomes that function to protect DNA from deterioration or fusion with neighboring chromosomes. TERRA has been shown to be ubiquitously expressed in almost all cell types containing linear chromosomes - including humans, mice, and yeasts. While the exact function of TERRA is still an active area of research, it is generally believed to play a role in regulating telomerase activity as well as maintaining the heterochromatic state at the ends of chromosomes. TERRA interaction with other associated telomeric proteins has also been shown to help regulate telomere integrity in a length-dependent manner.
  Due to the breadth of roles in which TERRA is implicated for maintaining the genomic integrity at the ends of chromosomes, TERRA dysfunction has also been shown to be associated with a number of disease states, including a number of syndromes related to inappropriate telomere shortening and cellular aging, and the progression of cancer.
context_section_description: In general, long non-coding RNAs are known to mediate epigenetic changes on chromatin by functioning as recruiters for chromatin-modifying enzymes to genomic loci. TERRA is thought to play a similar role, recruiting both heterochromatic proteins and associated chromatin-remodeling complexes to telomeres, helping to establish or maintain heterochromatin formation. 
  One manner in which chromatin maintains its condensed hetererochromatic state at the telomere is through the enzymes DNA methyltransferases 1 and 3b (DNMT1/3b). Experiments where these factors have been depleted result in increased TERRA expression levels, suggesting that methylation status of the subtelomeric region may help to regulate the expression of TERRA. Further post-translational modifications of telomeric histones may also play a pivotal role in TERRA regulation. Decreased density of trimethylated histones H3K9me3 and H4K30me3 have been shown to correlate with increased TERRA levels. RNA pulldown experiments have also shown that TERRA associates with heterochromatin proteins, including HP1α, HP1β, and the origin recognition complex (ORC). These factors are known to play a role in establishment of heterochromatin and subsequent transcriptional silencing. TERRA-mimicking oligonucleotides have also been shown to associate with other chromatin remodeling complexes such as the NuA Histone Acetyltransferase Complex, BAF-Type SWI/SNF Nucleosome Remodeling Complex, and the NoRC Chromatin Remodeling Complex. It is believed that TERRA may work to stabilize the interaction of these factors with chromatin to promote heterochromatin formation.
  Overall, evidence has shown a complex relationship whereby TERRA can both regulate the heterochromatic state and be regulated by the heterochromatic state. Increased density of repressive histone marks that cause chromatin to become more condensed correlate with observed decreases in TERRA expression. Concurrently, epigenetic changes that result in chromatin becoming more euchromatic or "open" in nature correlates with increased TERRA expression. Listed above are factors shown to contribute to modulating TERRA expression, but this is by no means an exhaustive list.
caption: Relative TERRA Expression by Heterochromatic State, with Examples of Contributing Modifiers
exif: {"Image Orientation": "Horizontal (normal)", "Image XResolution": "72", "Image YResolution": "72", "Image ResolutionUnit": "Pixels/Inch", "Image ExifOffset": "90", "EXIF ExifImageWidth": "2722", "EXIF ExifImageLength": "1530"}