HOXA-AS2 Epigenetically Inhibits HBV Transcription by Recruiting the MTA1-HDAC1/2 Deacetylase Complex to cccDNA Minichromosome.
HOXA‐AS2
Hepatitis B virus
MTA1‐HDAC1/2 deacetylase complex
cccDNA
self‐limiting HBV replication
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
22 Apr 2024
22 Apr 2024
Historique:
revised:
27
03
2024
received:
18
09
2023
medline:
22
4
2024
pubmed:
22
4
2024
entrez:
22
4
2024
Statut:
aheadofprint
Résumé
Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non-coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation. In this study, lncRNA sequencing (lncRNA seq) is conducted on five pairs of HBV-positive and HBV-negative liver tissue. Through analysis, HOXA-AS2 (HOXA cluster antisense RNA 2) is identified as a significantly upregulated lncRNA in HBV-infected livers. Further experiments demonstrate that HBV DNA polymerase (DNA pol) induces HOXA-AS2 after establishing persistent high-level HBV replication. Functional studies reveal that HOXA-AS2 physically binds to cccDNA and significantly inhibits its transcription. Mechanistically, HOXA-AS2 recruits the MTA1-HDAC1/2 deacetylase complex to cccDNA minichromosome by physically interacting with metastasis associated 1 (MTA1) subunit, resulting in reduced acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) associated with cccDNA and subsequently suppressing cccDNA transcription. Altogether, the study reveals a mechanism to self-limit HBV replication, wherein the upregulation of lncRNA HOXA-AS2, induced by HBV DNA pol, can epigenetically suppress cccDNA transcription.
Identifiants
pubmed: 38647380
doi: 10.1002/advs.202306810
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2306810Subventions
Organisme : National Key R&D Program of China
ID : 2022YFA1303600
Organisme : National Natural Science Foundation of China
ID : U23A20472
Organisme : National Natural Science Foundation of China
ID : 82273423
Organisme : National Natural Science Foundation of China
ID : 82302507
Organisme : National Natural Science Foundation of China
ID : 82202501
Organisme : National Natural Science Foundation of China
ID : 81802015
Organisme : Chongqing Natural Science Foundation
ID : CSTB2023NSCQ-BHX0170
Organisme : Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864
Organisme : Chongqing Natural Science Foundation
ID : CSTB2023NSCQ-LZX0053
Organisme : Chongqing Natural Science Foundation
ID : cstc2021jcyj-msxm0957
Organisme : Science and Technology Research Project of Chongqing Municipal Education Commission
ID : KJQN202100429
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0082
Informations de copyright
© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.
Références
N. Sarfaraz, S. Somarowthu, M. J. Bouchard, J Med Virol 2023, 95, e28058.
M.‐H. Chang, S.‐L. You, C.‐J. Chen, C.‐J. Liu, C.‐M. Lee, S.‐M. Lin, H.‐C. Chu, T.‐C. Wu, S.‐S. Yang, H.‐S. Kuo, D.‐S. Chen, J Natl Cancer Inst 2009, 101, 1348.
H. B. El‐Serag, Gastroenterology 2012, 142, 1264.
M. B. Zeisel, J. Lucifora, W. S. Mason, C. Sureau, J. Beck, M. Levrero, M. Kann, P. A. Knolle, M. Benkirane, D. Durantel, M.‐L. Michel, B. Autran, F.‐L. Cosset, H. Strick‐Marchand, C. Trépo, J.‐H. Kao, F. Carrat, K. Lacombe, R. F. Schinazi, F. Barré‐Sinoussi, J.‐F. Delfraissy, F. Zoulim, Gut 2015, 64, 1314.
H. Alter, T. Block, N. Brown, A. Brownstein, C. Brosgart, K.‐M. Chang, P.‐J. Chen, F. V. Chisari, C. Cohen, H. El‐Serag, J. Feld, R. Gish, J. Glenn, T. Greten, H. Guo, J.‐T. Guo, Y. Hoshida, J. Hu, K. V. Kowdley, W. Li, J. Liang, S. Locarnini, A. S. Lok, W. Mason, B. McMahon, A. Mehta, R. Perrillo, P. Revill, C. M. Rice, J. Rinaudo, et al., Hepatology 2018, 67, 1127.
A. Zhu, X. Liao, S. Li, H. Zhao, L. Chen, M. Xu, X. Duan, J Clin Transl Hepatol 2019, 7, 258.
X. Hong, E. S. Kim, H. Guo, Hepatology 2017, 66, 2066.
G. S. Laurent, C. Wahlestedt, P. Kapranov, Trends Genet 2015, 31, 239.
X. Liu, X. Duan, J. A. Holmes, W. Li, S. H. Lee, Z. Tu, C. Zhu, S. Salloum, A. Lidofsky, E. A. Schaefer, D. Cai, S. Li, H. Wang, Y. Huang, Y. Zhao, M.‐L. Yu, Z. Xu, L. Chen, J. Hong, W. Lin, R. T. Chung, Hepatology 2019, 69, 1004.
M. Morlando, A. Fatica, Int J Mol Sci 2018, 19, 570.
K. C. Wang, H. Y. Chang, Mol. Cell 2011, 43, 904.
M.‐C. Tsai, O. Manor, Y. Wan, N. Mosammaparast, J. K. Wang, F. Lan, Y. Shi, E. Segal, H. Y. Chang, Science 2010, 329, 689.
C. Chu, K. Qu, F. L. Zhong, S. E. Artandi, H. Y. Chang, Mol Cell 2011, 44, 667.
R. A. Gupta, N. Shah, K. C. Wang, J. Kim, H. M. Horlings, D. J. Wong, M.‐C. Tsai, T. Hung, P. Argani, J. L. Rinn, Y. Wang, P. Brzoska, B. Kong, R. Li, R. B. West, M. J. van de Vijver, S. Sukumar, H. Y. Chang, Nature 2010, 464, 1071.
P. Fang, H. Chen, Z. Ma, C. Han, W. Yin, S. Wang, H. Zhu, W. Xia, J. Wang, L. Xu, T. Liu, R. Yin, Cancer Commun. 2021, 41, 596.
K. K. Aneja, Y. Yuan, Front Microbiol 2017, 8, 613.
Y. Sun, Y. Teng, L. Wang, Z. Zhang, C. Chen, Y. Wang, X. Zhang, P. Xiang, X. Song, J. Lu, N. Li, L. Gao, X. Liang, Y. Xia, Z. Wu, C. Ma, Adv Sci. 2022, 9, e2103135.
D. Salerno, L. Chiodo, V. Alfano, O. Floriot, G. Cottone, A. Paturel, M. Pallocca, M.‐L. Plissonnier, S. Jeddari, L. Belloni, M. Zeisel, M. Levrero, F. Guerrieri, Gut 2020, 69, 2016.
C. Bolukbas, F. F. Bolukbas, M. Horoz, M. Aslan, H. Celik, O. Erel, BMC Infect Dis 2005, 5, 95.
T. Severi, C. Ying, J. R. Vermeesch, D. Cassiman, L. Cnops, C. Verslype, J. Fevery, L. Arckens, J. Neyts, J. F. van Pelt, Mol Cell Biochem 2006, 290, 79.
T. Mondal, S. Subhash, R. Vaid, S. Enroth, S. Uday, B. Reinius, S. Mitra, A. Mohammed, A. R. James, E. Hoberg, A. Moustakas, U. Gyllensten, S. J. M. Jones, C. M. Gustafsson, A. H. Sims, F. Westerlund, E. Gorab, C. Kanduri, Nat Commun 2015, 6, 7743.
A. Postepska‐Igielska, A. Giwojna, L. Gasri‐Plotnitsky, N. Schmitt, A. Dold, D. Ginsberg, I. Grummt, Mol Cell 2015, 60, 626.
V. B. O'Leary, S. V. Ovsepian, L. G. Carrascosa, F. A. Buske, V. Radulovic, M. Niyazi, S. Moertl, M. Trau, M. J. Atkinson, N. Anastasov, Cell Rep 2015, 11, 474.
S. Geisler, J. Coller, Nat Rev Mol Cell Biol 2013, 14, 699.
J. Zhao, T. K. Ohsumi, J. T. Kung, Y. Ogawa, D. J. Grau, K. Sarma, J. J. Song, R. E. Kingston, M. Borowsky, J. T. Lee, Mol. Cell 2010, 40, 939.
S. Guil, M. Soler, A. Portela, J. Carrère, E. Fonalleras, A. Gómez, A. Villanueva, M. Esteller, Nat Struct Mol Biol 2012, 19, 664.
Y.‐L. Yao, W.‐M. Yang, J Biol Chem 2003, 278, 42560.
Y.‐T. Li, C.‐J. Liu, J.‐H. Kao, L.‐F. Lin, H.‐C. Tu, C.‐C. Wang, P.‐H. Huang, H.‐R. Cheng, P.‐J. Chen, D.‐S. Chen, H.‐L. Wu, Hepatology 2023, 77, 379.
T. Zhang, G. Wei, C. J. Millard, R. Fischer, R. Konietzny, B. M. Kessler, J. W. R. Schwabe, N. Brockdorff, Nat Commun 2018, 9, 3798.
X. Li, B. Yuan, M. Lu, Y. Wang, N. Ding, C. Liu, M. Gao, Z. Yao, S. Zhang, Y. Zhao, L. Xie, Z. Chen, Nat Commun 2021, 12, 7213.
Z. Qi, G. Li, H. Hu, C. Yang, X. Zhang, Q. Leng, Y. Xie, D. Yu, X. Zhang, Y. Gao, K. Lan, Q. Deng, J Virol 2014, 88, 8045.
X. Zhao, H. Fan, X. Chen, X. Zhao, X. Wang, Y. Feng, M. Liu, S. Li, H. Tang, Hepatology 2021, 73, 503.
S. Bagga, S. Rawat, M. Ajenjo, M. J. Bouchard, Virology 2016, 498, 9.
D. Eckert, S. Buhl, S. Weber, R. Jäger, H. Schorle, Genome Biol 2005, 6, 246.
E. Van Otterloo, I. Milanda, H. Pike, J. A. Thompson, H. Li, K. L. Jones, T. Williams, Elife 2022, 11, e70511.
T. Pollicino, L. Belloni, G. Raffa, N. Pediconi, G. Squadrito, G. Raimondo, M. Levrero, Gastroenterology 2006, 130, 823.
Y. Feng, S. Hu, L. Li, X. Peng, F. Chen, Cell Death Dis 2020, 11, 1025.
M. Xie, M. Sun, Y. Zhu, R. Xia, Y. Liu, J. Ding, H. Ma, X. He, Z. Zhang, Z. Liu, X. Liu, W. De, Oncotarget 2015, 6, 33587.
J. Ding, M. Xie, Y. Lian, Y. Zhu, P. Peng, J. Wang, L. Wang, K. Wang, Oncogenesis 2017, 6, e288.
X. Yang, Y. Zhang, Y. Chen, X. He, Y. Qian, S. Xu, C. Gao, C. Mo, S. Chen, Q. Xiao, J Neuroinflammation 2021, 18, 197.
F. Chen, J. Chen, L. Yang, J. Liu, X. Zhang, Y. Zhang, Q. Tu, D. Yin, D. Lin, P.‐P. Wong, D. Huang, Y. Xing, J. Zhao, M. Li, Q. Liu, F. Su, S. Su, E. Song, Nat Cell Biol 2019, 21, 498.
C.‐M. Wong, F. H.‐C. Tsang, I. O.‐L. Ng, Nat Rev Gastroenterol Hepatol 2018, 15, 137.
B. Rehermann, M. Nascimbeni, Nat Rev Immunol 2005, 5, 215.
S. Yuan, G. Liao, M. Zhang, Y. Zhu, K. Wang, W. Xiao, C. Jia, M. Dong, N. Sun, A. Walch, P. Xu, J. Zhang, Q. Deng, R. Hu, J Hepatol 2021, 75, 74.
L. Belloni, L. Allweiss, F. Guerrieri, N. Pediconi, T. Volz, T. Pollicino, J. Petersen, G. Raimondo, M. Dandri, M. Levrero, J. Clin. Invest. 2012, 122, 529.
C. Chu, J. Quinn, H. Y. Chang, J Vis Exp 2012, 61, 3912.
B. M. Gyori, G. Venkatachalam, P. S. Thiagarajan, D. Hsu, M.‐V. Clement, Redox Biol 2014, 2, 457.