Disruption of CTCF-YY1-dependent Looping of the Human Papillomavirus Genome Activates Differentiation-induced Viral Oncogene Transcription

Overview

Journal PLoS Biol

Specialty Biology

Date 2018 Oct 26

PMID 30359362

Citations 45

Authors

Ieisha Pentland

Karen Campos-Leon

Marius Cotic

Kelli-Jo Davies

C David Wood

Ian J Groves

Megan Burley

Nicholas Coleman

Joanne D Stockton

Boris Noyvert

Andrew D Beggs

Michelle J West

Sally Roberts

Joanna L Parish

Affiliations

Soon will be listed here.

Abstract

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.

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