Histone Acetyltransferases (HATs)

Histone acetyltransferases (HATs) are the workhorses of the epigenome. These enzymes have a huge role epigenetic regulation of gene expression. They catalyze the transfer of an acetyl group from acetyl-CoA to ε-amino group of a histone lysine residue. These acetylations then serve allow transcriptional access to DNA by either neutralizing the positive histone charge, or serving as a binding site for chromatin remolding complexes.

Lys-CoA
TH 1834
1243583-85-8
MG149
1243583-85-8
NU 9056
1450644-28-6
L002
321695-57-2
B0084-370250
C646
328968-36-1
CPTH2
357649-93-5
Garcinol
78824-30-3

Background


An Overview of HATs

Histone modified enzyme-like remodeling complexes affect transcription by covalent modification of histone proteins. It causes changes in the structure and function of cells, tissues, organs, and even the whole organism, leading to the occurrence of diseases. Currently known modifications include methylation, acetylation, phosphorylation, ubiquitin, and ADP-ribose. In particular, acetylation plays an important role in the change of chromatin structure and the regulation of transcription. Histone acetyltransferases (HATs) regulate the acetylation of histone by modifying the acetylation of the core histone, which regulates the transcription of genes, participates in gene expression, and mediates the activation or silencing of genes. The high level of protein acetylation is often associated with gene activation, while the low level of histone acetylation is closely related to the inhibition of gene activity.

Major types of HATs

There are 5 types of hats-active proteins so far: 1) GCN5-related N- acetyltransferase family, including GCN5 and p300/CBP (CREB-binding protein)-associated factor (PCAF), which have bromine domains and can acetylate lysine residues on histone H2A (Lys5), H3 (Lys14) and H4 (Lys5 /8 /12 /16). 2) MYST family, including Monocytic Leukemia Zinc Finger Protein (MOZ) and Tat interaction protein, 60kD (Tip60), all have acetyl coenzyme A binding structure and zinc finger structure. 3) Cyclic Adenosine monophosphate (cAMP) response element binding protein p300/CBP family, a complementary activator of transcription factor complex. 4) the ordinary transcription factor histone acetylase. 5) Hormone related histone acetylase.

Inhibition of HATs

HATs inhibitors are expected to become a new class of drugs because they regulate transcription and produce antiviral, anti-inflammatory and antioxidant effects. For example, C646 is an inhibitor of HATs, which mainly inhibits p300 by preferentially acting on p300 compared with other acetyltransferases. In addition, Anacardic Acid is an effective inhibitor of p300 and p300/CBP-related factor HATs, with antibacterial and antimicrobial activities. MG149 is the most potent HATs inhibitor, which mainly acts on Tip60 and MOF.

HATs and diseases

HATs activity is associated with tumorss, for example, p300/CBP plays transcriptional regulation role in Wilms' tumor 1 (WT1). HATs p300 also has an effect on the migration of human breast cancer cells. In addition, Tip60 gene can cause osteosarcoma cells.

References:

1. Aquea, F., Timmermann, T., & Herrera-Vásquez, A. (2017). Chemical inhibition of the histone acetyltransferase activity in Arabidopsis thaliana. Biochemical and biophysical research communications, 483(1), 664-668.

2. Santer, F. R., Höschele, P. P., Oh, S. J., Erb, H. H., Bouchal, J., Cavarretta, I. T., ... & Culig, Z. (2011). Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Molecular cancer therapeutics.

3. Jha, S., Pol, S. V., Banerjee, N. S., Dutta, A. B., Chow, L. T., & Dutta, A. (2010). Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Molecular cell, 38(5), 700-711.