Журнал "Гастроэнтерология" Том 59, №1, 2025

На основі аналізу літературних джерел бази даних Pubmed, MedLine, The Cochrane Library, EMBASE автори статті наводять загальні положення стосовно ацетилювання гістонів. Автори акцентують увагу, що саме ацетилювання лізинового залишку є ключовою посттрансляційною модифікацією гістонів епігенетичними механізмами регуляції експресії генів. На сьогодні ідентифіковано не менше ніж 2000 білків людини, які можуть бути модифіковані за залишками лізину за допомогою ацетилювання. Близько 1000 білків у тканині печінки людини піддаються модифікації ацетилюванням лізину. Ацетилювання опосередковується гістоновими ацетилтрансферазами (histone acetyl transferases — HAT/KAT) і зазвичай пов’язане з активною транскрипцією гена через його здатність деконденсувати хроматин. Навпаки, гістонові деацетилази (histone deacetylases — HDAC/KDAC) видаляють ацетильну групу з лізинового залишку гістонів і таким чином відновлюють компактну форму хроматину. Стан ацетилювання таргетних сайтів визначається балансом активності між процесами ацетилювання та деацетилювання N-термінальних регіонів молекул гістонів. Гіперацетилювання гістонів може бути обумовлено як підвищенням активності HAT/KAT, так і зниженням експресії HDAC. Гістонові ацетилтрансферази каталізують перенесення ацетильної групи з ацетил-КоА на епсилон-аміногрупу лізину, нейтралізуючи позитивний заряд лізину та послаблюючи взаємодію між гістонами та молекулою ДНК. Ацетилювання гістонів завжди асоційоване з відкриттям хроматину та активацією транскрипції генів. Автори наголошують, що збільшення представництва ацетильованих маркерів пов’язане з прогресуванням метаболічно асоційованої жирової хвороби печінки (МАЖХП). Особливо високий рівень ацетилювання (гіперацетилювання) при розвитку МАЖХП відзначається на сайтах K9, K14 та K18 гістону 3. На сьогодні епігенетичні механізми, що визначають стан ацетилювання гістонів у ділянці певних генів, розглядаються як потенційні мішені для медикаментозного впливу. Вивчення впливу ацетилювання гістонів на морфологічні зміни тканини та розвиток метаболічних розладів є підґрунтям, що дозволить розробити ефективні епігенетичні методи лікування хворих на МАЖХП.

Based on the analysis of literature sources from the Pubmed, MEDLINE, The Cochrane Library, Embase databases, the authors of the article highlight general provisions regarding histone acetylation. They emphasize that it is acetylation of the lysine residue that is the key post-translational modification of histones by epigenetic mechanisms of gene expression regulation. To date, at least 2000 human proteins have been identified that can be modified at lysine residues by acetylation. About 1000 proteins in human liver tissue undergo modification by lysine acetylation. Acetylation is mediated by histone acetyltransferases (HAT/KAT) and is usually associated with active gene transcription due to its ability to decondense chromatin. In contrast, histone deacetylases (HDAC/KDAC) remove the acetyl group from the lysine residue of histones and, thus, restore the compact form of chromatin. The acetylation state of target sites is determined by the balance of activity between the processes of acetylation and deacetylation of the N-terminal regions of histone molecules. Histone hyperacetylation can be caused by both increased HAT/KAT activity and decreased HDAC expression. Histone acetyltransferases catalyze the transfer of an acetyl group from acetyl-CoA to the epsilon-amino group of lysine, neutralizing the positive charge of lysine and weakening the interaction between histones and the DNA molecule. Histone acetylation is always associated with chromatin opening and activation of gene transcription. The authors emphasize that an increase in the representation of acetylated markers is associated with the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). A particularly high level of acetylation (hyperacetylation) in MAFLD is noted at sites K9, K14 and K18 of histone 3. Today, epigenetic mechanisms that determine the state of histone acetylation in the region of certain genes are considered as potential targets for drug treatment. Studying the influence of histone acetylation on morphological changes in tissue and the development of metabolic disorders is the basis that will allow developing effective epigenetic methods for treatment of patients with MAFLD.

ожиріння; метаболічно асоційована жирова хвороба печінки; ацетилювання гістонів

obesity; metabolic dysfunction-associated fatty liver disease; histone acetylation

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