直接HBx基因组靶的全基因组鉴定。

StephenW

BMC Genomics. 2017 Feb 17;18(1):184. doi: 10.1186/s12864-017-3561-5.
Genome-wide identification of direct HBx genomic targets.Guerrieri F1, Belloni L1, D'Andrea D2, Pediconi N3, Le Pera L1,2, Testoni B4, Scisciani C5, Floriot O4, Zoulim F4, Tramontano A1,2,6, Levrero M7,8,9,10.
Author information

• 1Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy.
• 2Biocomputing Lab, Department of Physics, Sapienza University, Rome, Italy.
• 3Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, Rome, 00161, Italy.
• 4INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France.
• 5Department of Internal Medicine - DMISM, Sapienza University, Viale del Policlinico 155, 00161, Rome, Italy.
• 6Istituto Pasteur Fondazione Cenci Bolognetti, Viale Regina Elena 291, Rome, 00161, Italy.
• 7Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy. [email protected].
• 8INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France. [email protected].
• 9Department of Internal Medicine - DMISM, Sapienza University, Viale del Policlinico 155, 00161, Rome, Italy. [email protected].
• 10Cancer Research Center of Lyon (CRCL) - INSERM U1052, 151 cours Albert Thomas, 69424, Lyon Cedex 03, France. [email protected].
  

AbstractBACKGROUND: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV.
RESULTS: ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication.
CONCLUSIONS: Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication.


KEYWORDS: ChIP-Seq; Epigenetics; HBx; Hepatitis B virus; miRNAs

PMID:28212627DOI:10.1186/s12864-017-3561-5

StephenW

BMC基因组学。 2017 Feb 17; 18（1）：184。 doi：10.1186 / s12864-017-3561-5。
直接HBx基因组靶的全基因组鉴定。
Guerrieri F1，Belloni L1，D'Andrea D2，Pediconi N3，Le Pera L1,2，Testoni B4，Scisciani C5，Floriot O4，Zoulim F4，Tramontano A1,2,6，Levrero M7,8,9,10。
作者信息

    1 Center for Life NanoScience @ Sapienza，Istituto Italiano di Tecnologia，Viale Regina Elena 291，Rome，00161，Italy。
    2Biocomputing Lab，Department of Physics，Sapienza University，Rome，Italy。
    3Department of Molecular Medicine，Sapienza University，Viale Regina Elena 291，Rome，00161，Italy。
    4INSERM U1052，Cancer Research Center of Lyon（CRCL），151 cours Albert Thomas，Lyon，69424，France。
    5内科医学 - DMISM，Sapienza大学，Viale del Policlinico 155，00161，罗马，意大利。
    6 Pasteur Fondazione Cenci Bolognetti，Viale Regina Elena 291，Rome，00161，Italy。
    7 Center for Life NanoScience @ Sapienza，Istituto Italiano di Tecnologia，Viale Regina Elena 291，Rome，00161，Italy。 [email protected]。
    8INSERM U1052，Cancer Research Center of Lyon（CRCL），151 cours Albert Thomas，Lyon，69424，France。 [email protected]。
    9内科医学部 - DMISM，Sapienza大学，Viale del Policlinico 155，00161，罗马，意大利。 [email protected]。
    里昂CT研究中心（CRCL） - INSERM U1052,151 courtes Albert Thomas，69424，Lyon Cedex 03，France。 [email protected]。

抽象
背景：

乙型肝炎病毒（HBV）HBx调节蛋白是HBV复制所必需的，参与HBV相关的癌发生。 HBx与染色质修饰酶和转录因子相互作用以调节组蛋白翻译后修饰并调节病毒cccDNA转录和细胞基因表达。为了鉴定由HBx直接靶向的基因和非编码RNA（ncRNA），我们进行了染色质免疫沉淀测序（ChIP-Seq）以分析在复制HBV的细胞中宿主细胞染色质上的HBV募集。
结果：

HBx结合片段的ChIP-Seq高通量测序用于在HBV复制细胞中获得跨越基因组的HBx结合位点的高分辨率，无偏差的作图。参与细胞代谢，染色质动力学和癌症的蛋白质编码基因和ncRNA与已知调节HBV复制的基因/ ncRNA一起在HBx靶标中富集。加强内吞作用（Ras相关的大脑（RAB）GTP酶家族）和自噬（自噬相关的（ATG）基因，beclin-1，miR-33a）和转录抑制的microRNAs的基因/ miRNA的直接转录激活138，miR-224，miR-576，miR-596），其直接靶向HBV pgRNA并且将抑制HBV复制，有助于HBx介导的HBV复制增加。
结论：

我们的HBx基因组宽染色质招聘的ChIP-Seq分析定义了HBx直接靶向的基因和ncRNA的库，并导致鉴定HBx正调节cccDNA转录和HBV复制的新机制。
关键词：

ChIP-Seq;表观遗传学; HBx;乙型肝炎病毒; miRNA

PMID：
    28212627
DOI：
    10.1186 / s12864-017-3561-5