The chromatin remodelling factor ATRX suppresses R-loops in transcribed telomeric repeats

ATRX is a chromatin remodelling factor found at a wide range of tandemly repeated sequences including telomeres (TTAGGG)n. Acquired mutations in ATRX are found in nearly all tumours which maintain their telomeres via the alternative lengthening of telomere (ALT) pathway and ATRX is known to suppress this pathway. Here we show that recruitment of ATRX to telomeric repeats is dependent on their number, their orientation and, critically, on their transcription. Importantly, the transcribed telomeric repeats form RNA-DNA hybrids (R-loops) whose abundance correlates with the recruitment of ATRX. Here we show loss of ATRX is also associated with an increase in R-loop formation. These findings suggest that the presence of ATRX at telomeres may reflect a central role in suppressing deleterious DNA secondary structures which form at transcribed telomeric repeats, and this may account for the increases in DNA damage, stalling of replication and homology directed repair previously observed upon loss of ATRX function. Overall design: ATRX ChIP-seq in Suv39h1/2 KO MEFs, WT MEF and WT erythroid foetal liver