Histone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation.
Histone acetylation and deacetylation are essential parts of gene regulation. These reactions are typically catalysed by enzymes with "histone acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity. Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, acetyl coenzyme A) to another. Deacetylation is simply the reverse reaction where an acetyl group is removed from a molecule.
Acetylated histones, octameric proteins that organize chromatin into nucleosomes, the basic structural unit of the chromosomes and ultimately higher order structures, represent a type of epigenetic marker within chromatin. Acetylation removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription. This relaxation can be reversed by deacetylation catalyzed by HDAC activity. Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed (tightly packed) DNA is referred to as heterochromatin. Condensation can be brought about by processes including deacetylation and methylation.
Nucleosomes are portions of double-stranded DNA (dsDNA) that are wrapped around protein complexes called histone cores. These histone cores are composed of 8 subunits, two each of H2A, H2B, H3 and H4 histones. This protein complex forms a cylindrical shape that dsDNA wraps around with approximately 147 base pairs. Nucleosomes are formed as a beginning step for DNA compaction that also contributes to structural support as well as serves functional roles. These functional roles are contributed by the tails of the histone subunits.
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Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers, parasitic and inflammatory diseases. To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones.
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh
Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...
Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...
EPFL2024
Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to ...