Role of the cellular factor CTCF in the regulation of bovine leukemia virus latency and three-dimensional chromatin organization

被引：5

作者：

Bellefroid, Maxime ^{[1
]}

Rodari, Anthony ^{[1
]}

Galais, Mathilde ^{[1
]}

Krijger, Peter H. L. ^{[2
,3
]}

Tjalsma, Sjoerd J. D. ^{[2
,3
]}

Nestola, Lorena ^{[1
]}

Plant, Estelle ^{[1
]}

Vos, Erica S. M. ^{[2
,3
]}

Cristinelli, Sara ^{[4
]}

Van Driessche, Benoit ^{[1
]}

Vanhulle, Caroline ^{[1
]}

Ait-Ammar, Amina ^{[1
]}

Burny, Arsene ^{[1
]}

Ciuffi, Angela ^{[4
]}

de Laat, Wouter ^{[2
,3
]}

Van Lint, Carine ^{[1
]}

机构：

[1] Univ Libre Bruxelles ULB, Dept Mol Biol DBM, Serv Mol Virol, B-6041 Gosselies, Belgium

[2] Hubrecht Inst KNAW, Oncode Inst, NL-3584 CT Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[4] Univ Lausanne, Lausanne Univ Hosp, Inst Microbiol, CH-1011 Lausanne, Switzerland

来源：

NUCLEIC ACIDS RESEARCH | 2022年 / 50卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

LONG TERMINAL REPEAT; CAMP-RESPONSIVE-ELEMENT; RNA-POLYMERASE-II; BINDING-SITE; GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSION; READ ALIGNMENT; IN-VITRO; ACTIVATION; PROMOTER;

D O I：

10.1093/nar/gkac107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bovine leukemia virus (BLV)-induced tumoral development is a multifactorial phenomenon that remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the provirus. Next, we showed that CTCF localized to regions of transitions in the histone modifications profile along the BLV genome and that it is implicated in the repression of the 5 ' Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3 ' LTR promoter activity. Finally, we demonstrated that BLV integration deregulated the host cellular 3D chromatin organization through the formation of viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.

引用

页码：3190 / 3202

页数：13

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