Brd/BET Proteins Influence the Genome-Wide Localization of the Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus Major Latency Proteins

Frontiers in Microbiology
Rishikesh LotkeThomas F Schulz

Abstract

The rhadinoviruses Kaposi's Sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus (MHV-68) persist in infected hosts in a latent state that is characterized by the absence of virus production and by restricted viral gene expression. Their major latency protein, the latency-associated nuclear antigen (kLANA for KSHV and mLANA for MHV-68), is essential for viral genome maintenance and replication and involved in transcriptional regulation. Both kLANA and mLANA interact with cellular chromatin-associated proteins, among them the Bromodomain and Extra Terminal domain (Brd/BET) proteins, which recruit cellular and viral proteins to acetylated histones through their bromodomains and modulate cellular gene expression. Brd/BET proteins also play a role in the tethering, replication, segregation or integration of a diverse group of viral DNA genomes. In this study we explored if Brd/BET proteins influence the localization of the LANAs to preferential regions in the host chromatin and thereby contribute to kLANA- or mLANA-mediated transcriptional regulation. Using ChIP-Seq, we revealed a genome-wide co-enrichment of kLANA with Brd2/4 near cellular and viral transcriptional start sites (TSS). Treatment with I-BET151, an inhibi...Continue Reading

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Citations

Jun 3, 2021·Microorganisms·Shimaa Hassan AbdelAziz SolimanFabio Verginelli
Aug 28, 2021·Biomolecules·Nieves Lara-Ureña, Mario García-Domínguez

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Datasets Mentioned

BETA
GM12878
GSE153244
1

Methods Mentioned

BETA
acetylation
histone acetylation
FCS
PCR
FACS
Immunoprecipitation
ChIP
ChIP-Seq
Assay
Feature Extraction

Software Mentioned

Multiple Em for Motif Elicitation ( MEME )
ChIP
eArray
Feature Extraction
FASTQ
igvtools
Excel
GraphPad Prism
Centrimo
SAM

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