Histone acetylation modifications involve histone acetylases (HATs) and deacetylases (HDACs), which are responsible for adding or removing acetyl groups from histones, and some can also modify other proteins to target specific gene promoters by interacting with transcription factors to form complexes, thereby regulating gene transcription. In this issue, Xiao Heng will introduce to you what are the histone acetylation modifying enzyme families and their positioning and functions.
Histone acetyltransferases (hat
HAT uses acetyl-CoA as a cofactor, and adds an acetyl group to the amino group of lysine to neutralize the positive charge on lysine, so that the overall positive charge of histones is reduced, and then the interaction between histones and DNA is weakened, and the accessibility of genes is increased. HAT is also known as lysine acetyltransferase (KAT). So far, about 30 types of HATs have been found in humans, which can be divided into two categories, type A and type B, mainly according to their subcellular localization, of which type A is further divided into 5 families according to their catalytic domains. Type A HATs are located in the nucleus and play a role in transcription-related histone acetylation of chromatin, while type B is present in the cytoplasm and acetylates newly synthesized histones and affects the structure of nucleosomes. The five families of type A HATs include the GNAT family, the MyST family, the CBP p300 family, and the transcription factor-related families TAF1 and TIF C90. The main members of the GNAT family are P300 CBP-related factor (PCAF), GNC5, and ELP3. The MyST family includes MoZ, MorF, HBO1, HMOF, YBF2, SAS3, SAS2, and TiP60, among others. 
Histone deacetylase (hdac
HDAC removes acetyl groups from lysine residues of histones and non-histones. Eighteen HDACs have been identified in humans and can be divided into two families based on their conserved deacetylase domains and their dependence on specific cofactors: the Zn2+-dependent deacetylase family, and the Nad+-dependent sirtuin protein family. The deacetylase family can be subdivided into class I (HDAC and 8), class II (HDAC and 10), and class IV (HDAC11) based on similarity to yeast deacetylase; Among them, class II enzymes are further divided into IIA class and IIIB class according to their domain composition. The sirtuin protein is classified as an HDAC-like. HDACs have relatively low substrate specificity, one HDAC can act on multiple substrates, or multiple HDACs can act on the same substrate, which usually bind to each other and interact with other enzymes to participate in the regulation of basic cellular functions such as cell proliferation, cell cycle, regeneration, apoptosis, and differentiation.
1) HDAC-like consists of a completely conserved deacetylase domain, which is widely expressed in different tissue cells, mainly located in the nucleus, and has strong deacetylase activity against histones. In addition, studies have shown that HDACs can also deacetylate non-histone proteins as well as transcriptional regulators to regulate their activity. For example, HDAC1 and 2 form complexes with NURD, transcriptional regulator sin3a, REST co-repressor (COREST), and the silk ** deacetylase complex (MIDAc); HDAC3 can be recruited into the SMRT N-Cor corepressor complex; HDAC8 differs from the previous one in that it acts alone and does not form large complexes.
2) The C-terminus of an HDAC-like contains a conserved deacetylase domain. Class IIA HDACs (HDACs and 9) contain a unique adaptor domain at the N-terminus that can serve as binding sites for some transcriptional regulatory signals. Class IIB HDACs (HDAC6 and 10) have a tail domain at the C-terminus; HDAC6 contains two deacetylase domains and a C-terminal zinc finger ubiquitin-binding domain, while HDAC10 has only one deacetylase domain and a leucine-rich repeat domain at its C-terminus. HDACs are usually found in the cytoplasm. Class IIA HDACs have very low enzymatic activity and may function as low-activity deacetylases, or a specific target may not yet be found. However, IIB class HDAC is less studied, and it is known that HDAC6 is involved in the deacetylation of tubulin, IFN R, etc., and is related to the regulation of liver metabolism.
3) HDAC-like includes only HDAC11, shares a catalytic domain with class and HDAC-like species, and is involved in the expression of DNA replication factors CDT1 and IL-10.
4) HDAC-like enzymes are widely conserved from many organisms from bacteria to humans, and the presence of NAD FAD-binding domains is its distinctive feature. Seven sirtuins proteins have been reported in humans. SIRT1 has the strongest histone deacetylase activity. In addition to the deacetylase function, sirtuins protein can also exhibit other enzymatic activities, such as sirt5 shows lysine desuccinylase and demalonylase activities. These enzymes may be present in the nucleus (SIRT1, SIRT2, SIRT3, SIRT6, and SIRT7), cytoplasm (SIRT1 and SIRT2), or mitochondria (SIRT3, SIRT4, and SIRT5). The above is the main content of this issue, mainly introducing the types, positioning and functions of histone acetylation and deacetylase, interested partners can have an in-depth understanding, in the next issue we will take you to see the pathophysiological impact of histone acetylation when there is an abnormality, welcome to continue to pay attention! Hanheng Biotech has been focusing on virus packaging for more than ten years, and can customize overexpression and interference vectors of epigenetic-related genes
References
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