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

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Disruption of CTCF-YY1 dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription. / Pentland, Ieisha; Campos Leon, Karen; Cotic, Marius; Davies, Kelli-Jo; Wood, C. David ; Groves, Ian; Burley, Megan; Coleman, Nicolas; Stockton, Joanne; Noyvert, Boris; Beggs, Andrew; West, Michelle; Roberts, Sally; Parish, Joanna.

In: PLoS Biology, Vol. 16, No. 10, e2005752, 25.10.2018.

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@article{aec0b586849c4d8299b83038c0af3b5e,
title = "Disruption of CTCF-YY1 dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription",
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 recruitment resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene upregulation during cellular differentiation results from YY1 downregulation, 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.",
author = "Ieisha Pentland and {Campos Leon}, Karen and Marius Cotic and Kelli-Jo Davies and Wood, {C. David} and Ian Groves and Megan Burley and Nicolas Coleman and Joanne Stockton and Boris Noyvert and Andrew Beggs and Michelle West and Sally Roberts and Joanna Parish",
year = "2018",
month = oct
day = "25",
doi = "10.1371/journal.pbio.2005752",
language = "English",
volume = "16",
journal = "PLoS Biol.",
issn = "1544-9173",
publisher = "Public Library of Science (PLOS)",
number = "10",

}

RIS

TY - JOUR

T1 - Disruption of CTCF-YY1 dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription

AU - Pentland, Ieisha

AU - Campos Leon, Karen

AU - Cotic, Marius

AU - Davies, Kelli-Jo

AU - Wood, C. David

AU - Groves, Ian

AU - Burley, Megan

AU - Coleman, Nicolas

AU - Stockton, Joanne

AU - Noyvert, Boris

AU - Beggs, Andrew

AU - West, Michelle

AU - Roberts, Sally

AU - Parish, Joanna

PY - 2018/10/25

Y1 - 2018/10/25

N2 - 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 recruitment resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene upregulation during cellular differentiation results from YY1 downregulation, 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.

AB - 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 recruitment resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene upregulation during cellular differentiation results from YY1 downregulation, 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.

U2 - 10.1371/journal.pbio.2005752

DO - 10.1371/journal.pbio.2005752

M3 - Article

C2 - 30359362

VL - 16

JO - PLoS Biol.

JF - PLoS Biol.

SN - 1544-9173

IS - 10

M1 - e2005752

ER -