Epigenetics

Epigenetics research delves into the molecular mechanisms that control gene expression and cellular traits without altering the underlying DNA sequence. One crucial aspect of this field is the role of small molecules, which act as powerful regulators of epigenetic modifications. These small compounds, typically comprising a few dozen to a few hundred atoms, have emerged as essential tools in understanding and manipulating the epigenome.

  • DNA Methylation Inhibitors: Small molecules like 5-azacytidine and 5-aza-2'-deoxycytidine are DNA methyltransferase inhibitors. They block the addition of methyl groups to DNA, leading to DNA demethylation. This can reactivate silenced genes, potentially offering therapeutic avenues for conditions like cancer.
  • HDAC inhibitors: HDACs remove acetyl groups from histone proteins, contributing to gene repression. Small molecule HDAC inhibitors, such as Vorinostat and Romidepsin, can reverse this process by increasing histone acetylation, allowing genes to be more accessible for transcription. These inhibitors are being explored for cancer therapy and other conditions.
  • Histone Methyltransferase Inhibitors: Small molecules like GSK126 inhibit specific histone methyltransferases, affecting histone methylation patterns. This can alter gene expression, making them promising candidates for cancer and other diseases with epigenetic dysregulation.
  • RNA Modulators: Small molecules can also target non-coding RNAs involved in epigenetic regulation. For instance, small molecules called small interfering RNAs (siRNAs) can be designed to target and degrade specific long non-coding RNAs, influencing gene expression.
  • Epigenetic Reader Domain Inhibitors: These small molecules target proteins that recognize and bind to specific epigenetic marks. Examples include inhibitors of bromodomain-containing proteins (BET inhibitors), which can disrupt gene regulation by interfering with protein-DNA interactions.

Small molecules in epigenetics research not only provide insights into the fundamental biology of gene regulation but also hold immense promise for developing novel therapeutics. Their ability to selectively modulate specific epigenetic marks and pathways has led to ongoing clinical trials and drug development efforts for various diseases, including cancer, neurological disorders, and inflammatory conditions. Understanding and harnessing the power of these small molecules is at the forefront of modern epigenetics research, offering new hope for precision medicine and targeted therapies.


3 key components involved in the regulation of epigenetic modifications

Epigenetics Writer

Epigenetics writers are enzymes responsible for adding chemical marks or modifications to DNA or histone proteins. These marks include DNA methylation (addition of methyl groups to DNA) and histone modifications (such as acetylation, methylation, phosphorylation, etc.).

Epigenetics Reader

Function: Epigenetics readers are proteins that can recognize and bind to specific epigenetic marks on DNA or histones. These reader proteins interpret the epigenetic code and facilitate downstream cellular processes, such as gene activation or repression.

Epigenetics Eraser

Function: Epigenetics erasers are enzymes responsible for removing or reversing epigenetic marks on DNA or histones. This process allows for the dynamic regulation of gene expression and the resetting of epigenetic states during various stages of development and in response to environmental changes.

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  1. Phoenixin-20 (PNX-20) is a bioactive peptide with hormone-like actions in vertebrates, and can stimulates hypothalamo-pituitary-gonadal hormones and regulate reproductive processes in mammals. Phoenixin-20 promotes neuronal mitochondrial biogenesis via CREB-PGC-1α pathway. Phoenixin-20 has anxiolytic effect.
  2. His-Pro is a dipeptide consisting of histidyl and proline.
  3. Peptide 401, a potent mast cell degranulating factor from bee venom, suppresses the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, and 5-HT).
  4. Amyloid beta (Aβ or Abeta) is a peptide of 36-C43 amino acids that is processed from the Amyloid precursor protein. Amyloid β-Peptide (1-42) human is a 42-amino acid peptide which plays a key role in the pathogenesis of Alzheimer disease.
  5. Dynorphin A (1-13) Acetate is a potent, endogenous ??-agonist.
  6. Angiotensin I is formed by the action of renin on angiotensinogen.
  7. LEP (116-130) (mouse) is an adipocyte-derived hormone that acts as a major regulator for food intake and energy homeostasis.
  8. Myelin Basic Protein (87-99) is a self-antigen in multiple sclerosis (MS).
  9. Angiotensin (1-7) is an endogenous peptide fragment that can be produced from Ang I or Ang II via endo- or carboxy-peptidases respectively.
  10. Angiotensin II (Ang II) is an octapeptide hormone that plays a central role in cardiovascular homeostasis.
  11. Angiotensin III is a hexapeptide formed as a result of a cleavage at the N-terminus of Angiotensin II, a key factor in the Renin-Angiotensin-Aldosterone (RAAS) system by angiotensinases located in red blood cells and the vascular beds of most tissues.
  12. Gap junction blocker

    Gap 26 is a connexin mimetic peptide, corresponding to residues 63-75 of connexin 43, which is a gap junction blocker.
  13. Gap junction blocker

    Gap 27 is a peptide derived from connexin 43 that is a selective gap junction blocker.
  14. Dynamin inhibitor

    Dynamin Inhibitory Peptide is a peptide inhibitor of the GTPase dynamin.
  15. PKA inhibitor

    PKA inhibitor fragment (6-22) amide is a synthetic peptide that acts as a protein kinase inhibitor.
  16. Secretin (human),gastrointestinal peptide that stimulates pancreatic and biliary secretion.
  17. Melanocyte stimulating hormone release inhibiting factor is an endogenous peptide fragment derived from cleavage of the hormone oxytocin, but having generally different actions in the body.
  18. PKC inhibitor

    PKC (19-36), pseudosubstrate peptide inhibitor of protein kinase C (IC50 = 0.18 uM).
  19. COG 133 is 299 amino acids long and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood.
  20. Angiotensin 1/2 (1-9) is a peptide (ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE-HIS) containing the amino acids 1-9 that are converted from Angiotensin I/II peptide.
  21. Anti-Inflammatory Peptide 1, belongs to the group of synthetic oligopeptides corresponding to a region of high amino-acid sequence similarity between uteroglobin and lipocortin I.
  22. Ca 2+ /Mg 2+ -ATPase inhibitor

    Glucagon (19-29) (human) is a potent Ca 2+ /Mg 2+ -ATPase inhibitor.
  23. Epidermal Growth Factor Receptor Peptide (985-996) exists on the cell surface and is activated by the binding of its specific ligands, including epidermal growth factor and transforming growth factor.
  24. Laminin (925-933) is a peptide derived from residues 925-933 of the laminin B1 chain that binds to the laminin receptor.
  25. Cadherin Peptide, avian, is a class of type-1 transmembrane proteins.
  26. Fas C- Terminal Tripeptide is a tri-peptide with the sequence AC-SER-LEU-VAL-OH.
  27. Myelin Basic Protein (68-82), guinea pig is a peptide.
  28. Protein Kinase C (19-31), this peptide derived from the pseudo-substrate regulatory domain of PKCa (residues 19-31) with a serine at position 25 replacing the wild-type alanine, it was used as protein kinase C substrate peptide for testing the protein kinase C activity.
  29. Acetyl Angiotensinogen (1-14),porcine, The protein encoded by the Angiotensinogen gene is known as pre-angiotensinogen or angiotensinogen precursor.
  30. Thrombin Receptor Activator for Peptide 5 (TRAP-5), coagulation factor II (thrombin) receptor is a G protein-coupled receptor involved in the regulation of thrombotic response.
  31. BNP (1-32), human is a brain natriuretic peptide secreted by the human heart in response to cardiac volume or pressure.
  32. Corticotropin Releasing Factor, bovine, neurotransmitter and CRF receptor antagonist.
  33. Parathyroid hormone (PTH) is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid, which is secreted by the chief cell of the parathyroid glands as a polypeptide containing 84 amino acids.
  34. Peptide YY (PYY) is a short (36-amino acid) peptide released by cells in the ileum and colon in response to feeding. It is also known as peptide tyrosine tyrosine or pancreatic peptide YY3-36.
  35. FLAG tag Peptide is a 8 amino acid peptide with an enterokinase-cleavage site used for the purification of recombinant proteins.
  36. Influenza Hemagglutinin (HA) Peptide is a tag peptide derived from an epitope of the influenza hemagglutinin protein.
  37. 14-3-3 protein Inhibitor

    Difopein, dimeric version of R18 peptide that binds to 14.3.3 proteins with high affinity.
  38. Bax inhibitor

    Bax inhibitor peptide P5, cell-permeable synthetic peptide inhibitor of Bax translocation to mitochondria; designed from Ku70, a protein that is suggested to suppress the mitochondrial translocation of Bax. Inhibits Bax-mediated apoptosis in vitro.
  39. Bax inhibitor

    Bax inhibitor peptide V5, cell-permeable synthetic peptide inhibitor of Bax translocation to mitochondria; designed from Ku70, a protein that is suggested to suppress the mitochondrial translocation of Bax. Inhibits Bax-mediated apoptosis in vitro.
  40. Bax inhibitor

    Bax inhibitor peptide, negative control, negative control peptide for the Bax inhibitor peptides V5 and P5 , which inhibit Bax translocation to mitochondria and Bax-mediated apoptosis in vitro.
  41. VGF-derived peptide

    TLQP 21, VGF-derived peptide; spans residues 556-576 of the precursor sequence.
  42. Amyloid b-peptide (42-1) (human), inactive control for Amyloid b (1-42) peptide.
  43. Amyloid b-Peptide (10-20) (human), soluble amyloid b-peptide fragment that is a substrate for gelatinase A/type IV collagenase/MMP-2 and APP secretase; cleaved between Lys16 and Leu17.
  44. Amyloid b-peptide (25-35) (human), fragment of human amyloid beta-peptide, functionally required for the neurotrophic and neurotoxic effects associated with Alzheimer's disease.
  45. Amyloid b-Peptide (12-28) (human), amyloid b-peptide fragment; minimum section required to bind to brain proteins.

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