5 Matching Annotations
  1. Nov 2020
    1. serotonin has another function: It can act as one of those molecular Post-it notes. Specifically, it can bind to a type of histone known as H3, which controls the genes responsible for transforming human stem cells (the forerunner of all kinds of cells) into serotonin neurons. When serotonin binds to the histone, the DNA unwinds, turning on the genes that dictate the development of a stem cell into a serotonin neuron, while turning off other genes by keeping their DNA tightly wound. (So stem cells that never see serotonin turn into other types of cells, since the genetic program to transform them into neurons is not activated.)

      Serotonin can bind to H3 Histone and cause stem cells to become serotonin neurons.

      This research led the same team to wonder if Dopamine might act in a similar way.

      The serotonin paper is here: https://pubmed.ncbi.nlm.nih.gov/30867594/

    2. To test that hypothesis, the researchers genetically modified H3 histones in rats by replacing the amino acid that dopamine attaches to with a different one it doesn’t react with. This stops dopaminylation from occurring. Withdrawal from cocaine is associated with changes in the readout of hundreds of genes involved in rewiring neural circuits and altering synaptic connections, but in the rats whose dopaminylation was prevented, these changes were suppressed. Moreover, neural impulse firing in VTA neurons was reduced, and they released less dopamine, showing that these genetic changes were indeed affecting the brain’s reward circuit operation. This might account for why people with substance use disorder crave drugs that boost dopamine levels in the brain during withdrawal. Finally, in subsequent tests, the genetically modified rats exhibited much less cocaine-seeking behavior

      Rats were genetically modified to decrease dopaminylation (modifying M3 so dopamine couldn't attach). This correlated to the Ventral Tegmental Area firing less (less cocaine impulse) and released less dopamine. This showed that these changes to H3, and subsequently the dopaminylation, did impact brain's reward circuit operation.

    3. they showed that the same enzyme that attaches serotonin to H3 can also catalyze the attachment of dopamine to H3 — a process, I learned, called dopaminylation.

      The same enzyme that helps serotonin bind to H3 can also help dopamine bind to H3.

      Paper found here: https://pubmed.ncbi.nlm.nih.gov/32273471/

    1. histone acetylation

      Allows for DNA binding proteins to interact with sites to activate gene transcription and alters the accessibility of chromatin.

  2. Apr 2020
    1. distance between Lys37 on each H3 tail and the active site ofMLL1SETwas ~60 Å, allowing active-site access to H3 K4 and K9,but not to H3K27

      this distance betwen K37 and K4 may be similar to 60A, so that H3K4 methylation is possible