CpG-island promoters drive transcription of human telomeres.
The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide-rich DNA islands, shared among multiple human chromosome ends, promote transcription of TERRA molecules. TERRA promoters sustain cellular expression of reporter genes, are located immediately upstream of TERRA transcription start sites, and are bound by active RNAPII in vivo. Finally, the identified promoter CpG dinucleotides are methylated in vivo, and cytosine methylation negatively regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology.
Dipartimento di Genetica e Microbiologia Adriano Buzzati-Traverso, Università di Pavia, 2700 Pavia, Italy.
Solomon G
SG
Nergadze
Benjamin O
BO
Farnung
Harry
H
Wischnewski
Lela
L
Khoriauli
Valerio
V
Vitelli
Raghav
R
Chawla
Elena
E
Giulotto
Claus M
CM
Azzalin
D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D011401:Promoter Regions, Genetic; D016615:Telomere / Q000235:genetics*; D014158:Transcription, Genetic