Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and
Xuemeng Zhou1, Tsz Wing Sam1, Ah Young Lee2
1Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, SAR, China.
Nature Communications
|November 10, 2021
Summary
Polymorphic endogenous retroviruses (ERVs) can regulate gene expression and influence phenotypes. This study reveals how a specific polymorphic ERV element affects epigenetics and gene activity, contributing to differences between mouse strains.
Area of Science:
- Genomics
- Epigenetics
- Molecular Biology
Background:
- Polymorphic endogenous retroviruses (ERVs) are integrated into genomes and can influence host gene activity.
- The precise mechanisms by which ERVs impact epigenomes, transcriptomes, and drive variation within species are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms of how polymorphic ERVs affect epigenetics and gene expression.
- To identify specific polymorphic ERV elements and their regulatory roles in driving intra-specific variation.
Main Methods:
- Utilized wildtype murine embryonic stem cells (mESCs) from diverse genetic backgrounds.
- Analyzed the impact of a polymorphic MMERGLN (GLN) element on H3K27ac enrichment and neighboring gene transcription.
- Identified thousands of potential polymorphic ERVs in mESCs and assessed their association with chromatin states and transcription.
Main Results:
- Discovered a polymorphic MMERGLN (GLN) element that regulates H3K27ac enrichment and neighboring gene transcription.
- Demonstrated that this element enhances Klhdc4 gene expression, affecting downstream stress response genes.
- Found thousands of polymorphic ERVs in mESCs, with some showing links between proviral activity and epigenetic/transcriptional states.
Conclusions:
- Polymorphic ERV-derived cis-regulatory elements contribute to differential phenotypes between mouse strains.
- These findings elucidate how polymorphic ERVs shape epigenomes and transcriptional networks, leading to phenotypic divergence.
More Related Videos
Related Concept Videos
01:37Epigenetic Regulation
3.2K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.2K
02:32Position-effect Variegation
6.7K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.7K
02:02Cis-regulatory Sequences
10.8K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
10.8K
02:30Genomic Imprinting and Inheritance
35.5K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
35.5K
02:57piRNA - Piwi-interacting RNAs
7.1K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.1K
02:23Master Transcription Regulators
7.2K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.2K