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

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Version 2 2023-06-12, 07:29
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journal contribution
posted on 2023-06-12, 07:29 authored by Ieisha Pentland, Karen Campos-León, Marius Cotic, Kelli-Jo Davies, David WoodDavid Wood, Ian J Groves, Megan Burley, Nicholas Coleman, Joanne D Stockton, Boris Noyvert, Andrew Beggs, Michelle WestMichelle West, Sally Roberts, Joanna L Parish
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.

Funding

Gene deregulation in lymphoma: uncovering mechanisms and pathways exploited by Epstein-Barr virus; G1700; LEUKAEMIA AND LYMPHOMA RESEARCH; 15024

History

Publication status

  • Published

File Version

  • Published version

Journal

PLoS Biology

ISSN

1544-9173

Publisher

Public Library of Science

Issue

10

Volume

16

Page range

1-28

Article number

e2005752

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Gene Expression Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-11-01

First Open Access (FOA) Date

2018-11-01

First Compliant Deposit (FCD) Date

2018-10-30

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