Histone Acetyltransferase Inhibitor Screening Kit (ab133099) provides a fast, fluorescence-based method for evaluating pCAF HAT inhibitors.
Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair (PubMed:20953179, PubMed:23653357, PubMed:31278053, PubMed:32081014). Coordinates histone production and acetylation via H4 promoter binding (PubMed:31278053). Acetylates histone H4 at 'Lys-5' (H4K5ac) and 'Lys-12' (H4K12ac) and, to a lesser extent, histone H2A at 'Lys-5' (H2AK5ac) (PubMed:11585814, PubMed:22615379). Drives H4 production by chromatin binding to support chromatin replication and acetylation. Since transcription of H4 genes is tightly coupled to S-phase, plays an important role in S-phase entry and progression (PubMed:31278053). Promotes homologous recombination in DNA repair by facilitating histone turnover and incorporation of acetylated H3.3 at sites of double-strand breaks (PubMed:23653357). In addition, acetylates other substrates such as chromatin-related proteins (PubMed:32081014). Acetylates also RSAD2 which mediates the interaction of ubiquitin ligase UBE4A with RSAD2 leading to RSAD2 ubiquitination and subsequent degradation (PubMed:31812350). (Microbial infection) Contributes to hepatitis B virus (HBV) replication by acetylating histone H4 at the sites of 'Lys-5' and 'Lys-12' on the covalently closed circular DNA (cccDNA) minichromosome leading to its accumulation within the host cell.
KAT1, HAT1, Histone acetyltransferase type B catalytic subunit, Histone acetyltransferase 1
Histone Acetyltransferase Inhibitor Screening Kit (ab133099) provides a fast, fluorescence-based method for evaluating pCAF HAT inhibitors.
Sample | n | mean | SD | C.V. |
---|---|---|---|---|
Sample HAT | n 16 | mean - | SD - | C.V. 3.2 |
Sample | n | mean | SD | C.V. |
---|---|---|---|---|
Sample HAT | n 16 | mean - | SD - | C.V. 4.4 |
Histone Acetyltransferase Inhibitor Screening Kit (ab133099) provides a fast, fluorescence-based method for evaluating pCAF HAT inhibitors.
The procedure is based on the ability of 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) to react with free thiol grious present after the acetylation reaction. The reaction of the CPM reacts these free thiol groups forms a highly fluorescent product that is detected using excitation and emission wavelengths of 360-390 nm and 450-470 nm, respectively.
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Histone acetyltransferase often abbreviated as HAT is an enzyme responsible for the acetylation of lysine residues in histone proteins. This process known as histone acetylation helps regulate gene expression by relaxing chromatin structure and making DNA more accessible for transcription. HATs include various families such as the GNAT and MYST families. These enzymes are expressed in many cell types and found both in the nucleus where they modify histones and in the cytoplasm where they can acetylate non-histone proteins. Histone acetyltransferase enzyme typically weighs approximately 55 to 120 kDa with variation depending on the specific member and isoform.
Histone acetyltransferases play a significant role in epigenetic regulation by altering chromatin dynamics. They are often part of large multiprotein complexes that are key to gene regulation and they influence various cellular processes such as DNA repair replication and transcription. By transferring an acetyl group from acetyl coenzyme A to histone tails HATs facilitate transcriptional activation. This action can be measured using a histone acetyltransferase assay which quantifies their activity providing insights into their impact on gene expression.
Histone acetyltransferases are central to several important pathways including the regulation of transcription by RNA polymerase II and the p53 signaling pathway. HATs collaborate with other proteins such as transcription factors and coactivators to modulate these pathways. For instance they can interact with transcription factors to guide gene-specific transcriptional activation. These interactions make HAT activity relevant in studying cellular responses to external signals and maintaining homeostasis.
Abnormal histone acetyltransferase activity relates to cancer and neurodegenerative diseases. In cancer aberrant HAT function can lead to dysregulated gene expression promoting tumorigenesis. Histone acetyltransferase inhibitors have emerged as potential therapeutic agents in cancer treatment. Additionally in neurodegenerative disorders such as Huntington's disease altered histone acetylation patterns disturb gene expression necessary for neuronal function. Proteins like HDACs (histone deacetylases) also play a major role here as they reverse HAT-induced acetylation offering a balance in the regulation of acetylation status.
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Effect of garcinol in HAT activity. An example of a known pCAF HAT inhibitor, garcinol, interfering with the assay.
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