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人类PAD4通过脱甲基清除来调节氨酸基素甲基化水平
Yanming Wang1, Joanna Wysocka, Joyce Sayegh
1Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
概括
人类丁氨酸减小酶4 (PAD4) 从素氨酸残留物中去除甲基,将其转化为氨酸. 这种表观遗传修饰调节了基因表达,特别是对雌激素敏感基因.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 基因组甲基化调节基因表达,但是去甲基化酶是未知的.
- 氨酸甲基化在基因质上与表观遗传基因调节有关.
研究的目的:
- 为了识别除甲基化基素氨酸残留物的酶.
- 调查丁丁氨酸脱胺酶4 (PAD4) 在素氨酸脱甲基化和基因调节中的作用.
主要方法:
- 使用人类PAD4.4的酶分析.
- 在HL-60颗粒细胞和MCF-7细胞中分析基因素修饰.
- 调查PAD4对基因素H3和H4甲基化和林化的影响.
主要成果:
- 人类PAD4被确定为一种将基因组甲基氨酸转化为氨酸的酶.
- PAD4 准 histones H3 和 H4 上的多个 arginine 位点,包括那些由 CARM1 和 PRMT1.1 甲基化的位点.
- 在HL-60细胞中,PAD4活性降低了素甲基化和增加了素化.
- PAD4活性与MCF-7细胞中雌激素响应基因的转录调节相关.
结论:
- PAD4通过调节基因氨酸甲基化和氨化调节基因表达.
- PAD4代表了一种新的表观遗传调节器,准了基因组氨酸基因的修饰.
相关概念视频
Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
pH Homeostasis
Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory Regulation of...
Respiratory Regulation of...
Acid-Base Balance
The human body maintains a narrow pH range regulated through acid-base balance. This balance is crucial as changes in the hydrogen ion concentration can disrupt cell membrane stability, alter protein structures, and change enzyme activities. The normal pH of arterial blood is 7.4, venous blood and interstitial fluid is 7.35, and intracellular fluid averages 7.0.
When the pH of arterial blood rises above 7.45, it results in a condition called alkalosis. Conversely, a drop below 7.35 leads to...
When the pH of arterial blood rises above 7.45, it results in a condition called alkalosis. Conversely, a drop below 7.35 leads to...
Respiratory Regulation of Acid-Base Balance
Respiratory compensation is a vital physiological process that stabilizes blood plasma pH by regulating the partial pressure of carbon dioxide (PCO2), a key determinant of pH levels. Most carbon dioxide in the blood dissolves and converts into carbonic acid (H2CO3). It dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3⁻). There is also an inverse relationship between PCO2 and pH.
When carbon dioxide levels increase in the blood, more H+ and HCO3⁻ are produced, leading to a...
When carbon dioxide levels increase in the blood, more H+ and HCO3⁻ are produced, leading to a...
Renal Regulation of Acid-Base Balance
Metabolic reactions in the body produce nonvolatile acids, such as sulfuric acid, which generate an acid load of approximately 1 mEq of H+ per kilogram of body weight daily. Excreting H+ in the urine is essential to balance this acid load.
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...
Compensation Mechanisms
The human body employs intricate mechanisms to counteract changes in blood pH, preventing conditions like acidosis (pH < 7.35) and alkalosis (pH > 7.45). These compensatory responses aim to restore normal arterial blood pH by engaging respiratory or renal systems, depending on the source of the imbalance.
Respiratory Compensation
This mechanism addresses metabolic-induced pH imbalances by adjusting breathing rates. Respiratory compensation begins within minutes of detecting a pH...
Respiratory Compensation
This mechanism addresses metabolic-induced pH imbalances by adjusting breathing rates. Respiratory compensation begins within minutes of detecting a pH...

