Details

Autor(en) / Beteiligte

• Pentland, Ieisha
• Campos-León, Karen
• Cotic, Marius
• Davies, Kelli-Jo
• Wood, C David
• Groves, Ian J
• Burley, Megan
• Coleman, Nicholas
• Stockton, Joanne D
• Noyvert, Boris
• Beggs, Andrew D
• West, Michelle J
• Roberts, Sally
• Parish, Joanna L
• Sugden, Bill

Titel

Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription

Ist Teil von

• PLoS biology, 2018-10, Vol.16 (10), p.e2005752

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• The complex life cycle of oncogenic human papillomavirus (HPV) initiates in undifferentiated basal epithelial keratinocytes where expression of the E6 and E7 oncogenes is restricted. Upon epithelial differentiation, E6/E7 transcription is increased through unknown mechanisms to drive cellular proliferation required to support virus replication. We report that the chromatin-organising CCCTC-binding factor (CTCF) promotes the formation of a chromatin loop in the HPV genome that epigenetically represses viral enhancer activity controlling E6/E7 expression. CTCF-dependent looping is dependent on the expression of the CTCF-associated Yin Yang 1 (YY1) transcription factor and polycomb repressor complex (PRC) recruitment, resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene up-regulation during cellular differentiation results from YY1 down-regulation, disruption of viral genome looping, and a loss of epigenetic repression of viral enhancer activity. Our data therefore reveal a key role for CTCF-YY1-dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis.