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Updated: Jul 18, 2025
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DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments
Published on: January 27, 2016
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Multivalency of nucleosome recognition by LEDGF.
Eliška Koutná1,2, Vanda Lux1, Tomáš Kouba1
1Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 160 00, Czech Republic.
Nucleic Acids Research
|August 24, 2023
Summary
The LEDGF PWWP domain recognizes both di- and trimethylated H3K36 histone marks. Intrinsically disordered regions of LEDGF interact with DNA, potentially influencing transcription regulation.
Area of Science:
- Molecular Biology
- Epigenetics
- Structural Biology
Background:
- Eukaryotic transcription relies on histone modifications recognized by chromatin readers.
- Mechanisms of discrimination between different histone modification states are not fully understood.
- The role of intrinsically disordered regions in nucleosome binding is largely unexplored.
Purpose of the Study:
- To elucidate the structural basis of H3K36 methylation recognition by the LEDGF PWWP domain.
- To investigate the role of intrinsically disordered regions of LEDGF in nucleosome and DNA interactions.
- To understand how LEDGF contributes to transcription elongation.
Main Methods:
- X-ray crystallography to determine the structure of LEDGF PWWP domain in complex with H3K36 di- and trimethylated nucleosomes.
- Biochemical assays to study DNA-binding properties of LEDGF intrinsically disordered regions.
- Analysis of dynamic interactions in dinucleosome contexts.
Main Results:
- The LEDGF PWWP domain recognizes both H3K36 di- and trimethylation similarly.
- A secondary interaction site for the PWWP domain was identified at the nucleosomal DNA interface.
- Intrinsically disordered regions of LEDGF contain DNA-interacting motifs that distinguish intra- vs. extranucleosomal DNA.
Conclusions:
- LEDGF utilizes its PWWP domain for H3K36 methylation recognition and an additional site for DNA interaction.
- Intrinsically disordered regions contribute to nucleosome binding and DNA discrimination.
- Multivalent interactions of LEDGF with chromatin may facilitate transcription elongation by recruiting factors to RNA polymerase II.
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