Related Experiment Video
Updated: May 15, 2025
09:16
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
7.3K
Intragenic viral silencer element regulates HTLV-1 latency via RUNX complex recruitment
Kenji Sugata1, Akhinur Rahman1, Koki Niimura1,2
1Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
Nature Microbiology
|May 13, 2025
Summary
Human T cell leukaemia virus type 1 (HTLV-1) uses a silencer region to achieve latency, unlike HIV-1. This mechanism, involving RUNX1 binding, aids HTLV-1 persistence and may offer therapeutic targets.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Retroviruses like HTLV-1 and HIV-1 integrate into host genomes for persistent infections.
- HTLV-1 establishes latency and can cause leukaemia, while HIV-1 causes immune collapse.
- Mechanisms for HTLV-1's latency preference are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms behind HTLV-1's latency.
- To identify host-viral interactions regulating HTLV-1 gene expression.
- To explore potential therapeutic strategies for HTLV-1 infection.
Main Methods:
- Analysis of blood samples from individuals with HTLV-1 infection.
- Identification and characterization of an open chromatin region within the HTLV-1 provirus.
- Investigating the role of host transcription factor RUNX1 binding.
Main Results:
- An open chromatin region within the HTLV-1 provirus acts as a transcriptional silencer, regulating viral expression.
- The host transcription factor RUNX1 binds to this silencer, repressing HTLV-1 replication.
- Mutating the silencer increases HTLV-1 replication and immunogenicity; its insertion into HIV-1 reduces viral production.
Conclusions:
- HTLV-1 employs a transcriptional silencer regulated by RUNX1 for long-term persistence.
- This mechanism highlights a key difference in infection strategies between HTLV-1 and HIV-1.
- The identified silencer represents a potential target for novel antiviral therapies.
More Related Videos
07:18High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
5.7K
13:47Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models
Published on: March 29, 2019
9.4K
Related Concept Videos
03:18Non-LTR Retrotransposons
11.3K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.3K
02:30siRNA - Small Interfering RNAs
16.3K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.3K
03:08LTR Retrotransposons
17.3K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
17.3K
02:36RNA Polymerase II Accessory Proteins
9.0K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.0K
02:04Co-activators and Co-repressors
7.2K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.2K
03:17Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K