Yin-Yang 1 and HBx protein activate HBV transcription by mediating the spatial interaction of cccDNA minichromosome with cellular chromosome 19p13.11

Shen, Congle; Feng, Xiaoyu; Mao, Tianhao; Yang, Di; Zou, Jun; Zao, Xiaobin; Deng, Qiang; Chen, Xiangmei; Lü, Fang

doi:10.1080/22221751.2020.1840311

Cited by 20 publications

(14 citation statements)

References 34 publications

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“…Contacts between HBV episomal DNA and cellular enhancers has also been observed using a 3C approach [66]. In this work, the authors identified a preferential interaction between HBV and the chromosome 19p13.11 region, which contains a highly active enhancer.…”

Section: Hbvmentioning

confidence: 75%

Crosstalk between Hepatitis B Virus and the 3D Genome Structure

Dias

Sarica

Cournac

et al. 2022

Viruses

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Viruses that transcribe their DNA within the nucleus have to adapt to the existing cellular mechanisms that govern transcriptional regulation. Recent technological breakthroughs have highlighted the highly hierarchical organization of the cellular genome and its role in the regulation of gene expression. This review provides an updated overview on the current knowledge on how the hepatitis B virus interacts with the cellular 3D genome and its consequences on viral and cellular gene expression. We also briefly discuss the strategies developed by other DNA viruses to co-opt and sometimes subvert cellular genome spatial organization.

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Section: Hbvmentioning

confidence: 75%

Crosstalk between Hepatitis B Virus and the 3D Genome Structure

Dias

Sarica

Cournac

et al. 2022

Viruses

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“…Moreover, 3C has been used to identify potential interactions of cccDNA and cellular chromatin through rcccDNA transfection in hepatoma cells and has been used to demonstrate that cccDNA is specifically associated with human chromosome 19p13.11 region. This region contains a highly active enhancer element that is mediated by cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx [ 37 ]. More importantly, circularized chromosome conformation capture (4C) sequencing analysis have revealed that transcriptionally inactive cccDNA preferentially accumulates at specialized areas, including regions close to chromosome 19 (chr.19).…”

Section: Discussionmentioning

confidence: 99%

PRKDC promotes hepatitis B virus transcription through enhancing the binding of RNA Pol II to cccDNA

2022

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Hepatitis B virus infection remains a major health problem worldwide due to its high risk of liver failure and hepatocellular carcinoma. Covalently closed circular DNA (cccDNA), which is present as an individual minichromosome, serves as the template for transcription of all viral RNAs and pla ays critical role in viral persistence. Therefore, there is an urgent need to gain broader insight into the transcription regulation of cccDNA. Here, we combined a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with an engineered ascorbate peroxidase 2 (APEX2) to identify cccDNA associated proteins systematically in living cells. By functional screening, we verified that protein kinase, DNA-activated, catalytic subunit (PRKDC) was an effective activator of HBV cccDNA transcription in HBV-infected HepG2-NTCP cells and primary human hepatocytes. Mechanismly, PRKDC interacted with POLR2A and POLR2B, the two largest subunits of RNA polymerase II (Pol II) and recruited Pol II to HBV cccDNA minichromosome in a kinase-dependent manner. PRKDC knockdown or inhibitor treatment significantly decreased the enrichment of POLR2A and POLR2B on cccDNA, as well as reducing the levels of cccDNA associated Pol II Ser5 and Ser2 phosphorylation, which eventually inhibited the HBV cccDNA activity. Collectively, these findings give us new insights into cccDNA transcription regulation, thus providing new potential targets for HBV treatment in patients.

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“…In addition, the HBx viral protein could enhance YY1 activity through the recruitment of HDAC [ 130 ]. It has been proven that HBx can interact with YY1 [ 131 ]. Other data revealed that YY1 can bind to the binding elements of the Sox4 promoter, thus stimulating its activity during HBV infection.…”

Section: Yy1—activator or Repressor Of Viral Expression?mentioning

confidence: 99%

Dual Role of YY1 in HPV Life Cycle and Cervical Cancer Development

Warowicka

Broniarczyk

Węglewska

et al. 2022

IJMS

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Human papillomaviruses (HPVs) are considered to be key etiological agents responsible for the induction and development of cervical cancer. However, it has been suggested that HPV infection alone may not be sufficient to promote cervical carcinogenesis, and other unknown factors might be required to establish the disease. One of the suggested proteins whose deregulation has been linked with oncogenesis is transcription factor Yin Yang 1 (YY1). YY1 is a multifunctional protein that is involved not only in the regulation of gene transcription and protein modification, but can also control important cell signaling pathways, such as cell growth, development, differentiation, and apoptosis. Vital functions of YY1 also indicate that the protein could be involved in tumorigenesis. The overexpression of this protein has been observed in different tumors, and its level has been correlated with poor prognoses of many types of cancers. YY1 can also regulate the transcription of viral genes. It has been documented that YY1 can bind to the HPV long control region and regulate the expression of viral oncogenes E6 and E7; however, its role in the HPV life cycle and cervical cancer development is different. In this review, we explore the role of YY1 in regulating the expression of cellular and viral genes and subsequently investigate how these changes inadvertently contribute toward the development of cervical malignancy.

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Yin-Yang 1 and HBx protein activate HBV transcription by mediating the spatial interaction of cccDNA minichromosome with cellular chromosome 19p13.11

Cited by 20 publications

References 34 publications

Crosstalk between Hepatitis B Virus and the 3D Genome Structure

Crosstalk between Hepatitis B Virus and the 3D Genome Structure

PRKDC promotes hepatitis B virus transcription through enhancing the binding of RNA Pol II to cccDNA

Dual Role of YY1 in HPV Life Cycle and Cervical Cancer Development

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