Related Experiment Video
Updated: May 2, 2026
09:14
DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments
Published on: January 27, 2016
17.8K
PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration
Christopher L Baker1, Michael Walker, Shimpei Kajita
1Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
Genome Research
|March 8, 2014
Summary
The PRDM9 protein guides genetic recombination hotspots in mammals by modifying histone H3. This process dictates where DNA double-strand breaks occur, controlling crossing-over during meiosis.
Area of Science:
- Genetics
- Molecular Biology
- Epigenetics
Background:
- Genetic recombination in mammals is confined to specific regions called hotspots.
- The protein PRDM9 is a key determinant of these hotspot locations.
- PRDM9 binds DNA and modifies histone H3 at lysine 4 (H3K4me3), facilitating double-strand break (DSB) formation.
Purpose of the Study:
- To investigate PRDM9-dependent histone modifications genome-wide.
- To understand how PRDM9 influences nucleosome organization and DSB formation.
- To elucidate the role of PRDM9 in defining meiotic recombination boundaries.
Main Methods:
- Genome-wide analyses of PRDM9-dependent histone modifications in two inbred mouse strains.
- In vitro confirmation of PRDM9 binding motif.
- Integration of genetic cross data.
Main Results:
- PRDM9 binding reorganizes nucleosomes, creating a nucleosome-depleted region centered on its binding motif.
- DSBs are precisely located over the PRDM9 binding motif within these depleted regions.
- Crossing-over events are restricted to H3K4me3-marked regions.
Conclusions:
- PRDM9 binding establishes nucleosome-depleted regions that direct DSB formation.
- H3K4me3 marks define the boundaries of meiotic recombination.
- PRDM9-modified nucleosomes play a critical role in regulating the location and extent of Holliday junction branch migration.
Related Concept Videos
02:13Cooperative Binding of Transcription Regulators
6.0K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.0K
02:13Cooperative Binding of Transcription Regulators
1.8K
1.8K
02:54Nucleosome Remodeling
8.7K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
8.7K
02:31Homologous Recombination
58.8K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
58.8K
02:38Heterochromatin
12.0K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
12.0K
02:37Restarting Stalled Replication Forks
5.1K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.1K