Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known...Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known, recent discoveries reveal that epigenetic processes are an integral part of ABA-regulated processes. Epigenetic mechanisms, namely, histone modifications and cytosine DNA methylation-induced modification of genome give rise to epigenomes, which add diversity and complexity to the genome of organisms. Histone monoubiquitination appears to regulate ABA levels in developing seeds through histone H2B monoubiquitination. ABA and H2B ubiquitination dependent chromatin remodeling regulate seed dormancy. Transcription factor networks necessary for seed maturation are repressed by histone deacetylases （HDACs）-dependent and PICKLE chromatin remodeling complexes （CRCs）, whereas ABA induces the expression of these genes directly or through repression of HDACs. Abiotic stress-induced ABA regulates stomatal response and stress- responsive gene expression through HDACs and HOS15-dependent histone deacetylation, as well as through the ATP- dependent SWITCH/SUCROSE NONFERMENTING CRC. ABA also probably regulates the abiotic stress response through DNA methylation and short interfering RNA pathways. Further studies on ABA-regulated epigenome will be of immense use to understand the plant development, stress adaptation and stress memory.展开更多
Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin stru...Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin structure and is associated with gene activation, whereas deacetylation of histone is often correlated with ＇closed＇ chromatin and gene repression. Histone deacetylation is catalyzed by histone deacetylases （HDACs）. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, and development in plants. Furthermore, HDACs were shown to interact with various chromatin remolding factors and transcription factors involved in transcriptional repression in multiple developmental processes. In this review, we summarized recent findings on the transcriptional repression mediated by HDACs in plants.展开更多
Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl ...Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl groups from lysines of both histone and non-histone proteins. While tremendous progress has been made in understanding the function and mechanism of HDACs in animals in the past two decades, nearly half of the HDAC studies in plants were reported within the past five years. In this review,we summarize the major findings on plant HDACs, with a focus on the model plant Arabidopsis thaliana, and highlight the components, regulatory mechanisms, and biological functions of HDAC complexes.展开更多
Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have o...Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient outcomes.More effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of neoplasm.Among new agents,histone deacetylase inhibitors (HDACIs) are now being tested.HDACIs have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and angiogenesis.HDACIs induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell lines.In the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are presented.HDACIs constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses.展开更多
目的探讨组蛋白脱乙酰基酶6（HDAC6）抑制剂Tubastatin A Hcl对急性支气管哮喘（简称哮喘）小鼠气管炎症的干预作用。方法48只BALB／C小鼠按随机数字表法随机分为正常组、哮喘组、地塞米松组和Tubastatin A Hcl组各12只。测定各组小鼠...目的探讨组蛋白脱乙酰基酶6（HDAC6）抑制剂Tubastatin A Hcl对急性支气管哮喘（简称哮喘）小鼠气管炎症的干预作用。方法48只BALB／C小鼠按随机数字表法随机分为正常组、哮喘组、地塞米松组和Tubastatin A Hcl组各12只。测定各组小鼠气管反应性，计数其支气管肺泡灌洗液（BALF）中细胞总数和分类细胞数以及白细胞介素（IL）-4、IL-5和γ干扰素（IFN-γ）水平。取各组小鼠肺组织分别通过HE染色观察气管炎症浸润、AB-PAS染色观察气管上皮杯状细胞化生、Masson染色观察肺组织胶原沉积情况。结果Tubastatin A Hcl组气管反应性显著低于哮喘组[（4．18±0．94）比（6．02±0．47），P〈0．05]；Tubastatin A Hcl组BALF中炎症细胞总数[（57．0±5．7）×10^4／ml比（87．0±5．6）×10^4／m1]、嗜酸性粒细胞数[（6．8±1．7）×10^4／ml比（12．3±3．5）×10^4／m1]、IL-4[（19．3±2．7）比（26．2±3．2）ng／ml]水平均显著低于哮喘组（均P〈0．05），IL-5低于哮喘组、IFN-γ水平高于哮喘组但差异均无统计学意义（均P〉0．05）；Tubastatin A Hcl组肺组织气管血管周围炎症细胞浸润程度、炎症细胞数[（9．80±2．42）比（20．67±7．53）个]、炎症评分[（2．20±0．70）比（3．60±0．68）分]、杯状细胞化生百分比[（50．46±5．03）％比（71．06±5．38）％]均显著低于哮喘组（均P〈0．05），胶原沉积面积低于哮喘组但差异无统计学意义（P〉0．05）。但上述结果地塞米松组均略优于TubastatinAHcl组但差异均无统计学意义（均P〉0．05）。结论Tubastatin A Hcl能够有效缓解急性期哮喘气管炎症水平，但其抗炎作用有限，效果并不如地塞米松显著。展开更多
Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed countries.Pancreatic cancer is difficult to diagnose,allow...Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed countries.Pancreatic cancer is difficult to diagnose,allowing few patients to have the necessary treatment at a relatively early stage.Despite a marginal benefit in survival,the overall response of pancreatic cancer to current systemic therapy continues to be poor,and new therapies are desperately needed.Histone deacetylase(HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors(HDACIs) have been shown to induce differentiation and cell cycle arrest,activate the extrinsic or intrinsic pathways of apoptosis,and inhibit invasion,migration and angiogenesis in different cancer cell lines.As a result of promising preclinical data,various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies.Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma.The use of HDACIs in clinical trials,in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed.Unfortunately,clinical data for HDACIs in patients with pancreatic cancer are inadequate,because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase Ⅱ/Ⅲ trials,among others with advanced solid tumors,is very limited.More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.展开更多
基金SERC Fact Track Scheme for Young Scientist, DST, Govt.of India, New Delhi to V. Chinnusamythe State Key Basic Researchand Development Plan of China (2003CB114300)the National Natural Science Foundation of China (30421002 and 30670182) to Z. Gong.
文摘Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known, recent discoveries reveal that epigenetic processes are an integral part of ABA-regulated processes. Epigenetic mechanisms, namely, histone modifications and cytosine DNA methylation-induced modification of genome give rise to epigenomes, which add diversity and complexity to the genome of organisms. Histone monoubiquitination appears to regulate ABA levels in developing seeds through histone H2B monoubiquitination. ABA and H2B ubiquitination dependent chromatin remodeling regulate seed dormancy. Transcription factor networks necessary for seed maturation are repressed by histone deacetylases （HDACs）-dependent and PICKLE chromatin remodeling complexes （CRCs）, whereas ABA induces the expression of these genes directly or through repression of HDACs. Abiotic stress-induced ABA regulates stomatal response and stress- responsive gene expression through HDACs and HOS15-dependent histone deacetylation, as well as through the ATP- dependent SWITCH/SUCROSE NONFERMENTING CRC. ABA also probably regulates the abiotic stress response through DNA methylation and short interfering RNA pathways. Further studies on ABA-regulated epigenome will be of immense use to understand the plant development, stress adaptation and stress memory.
文摘Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin structure and is associated with gene activation, whereas deacetylation of histone is often correlated with ＇closed＇ chromatin and gene repression. Histone deacetylation is catalyzed by histone deacetylases （HDACs）. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, and development in plants. Furthermore, HDACs were shown to interact with various chromatin remolding factors and transcription factors involved in transcriptional repression in multiple developmental processes. In this review, we summarized recent findings on the transcriptional repression mediated by HDACs in plants.
文摘Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl groups from lysines of both histone and non-histone proteins. While tremendous progress has been made in understanding the function and mechanism of HDACs in animals in the past two decades, nearly half of the HDAC studies in plants were reported within the past five years. In this review,we summarize the major findings on plant HDACs, with a focus on the model plant Arabidopsis thaliana, and highlight the components, regulatory mechanisms, and biological functions of HDAC complexes.
文摘Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient outcomes.More effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of neoplasm.Among new agents,histone deacetylase inhibitors (HDACIs) are now being tested.HDACIs have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and angiogenesis.HDACIs induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell lines.In the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are presented.HDACIs constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses.
文摘目的探讨组蛋白脱乙酰基酶6（HDAC6）抑制剂Tubastatin A Hcl对急性支气管哮喘（简称哮喘）小鼠气管炎症的干预作用。方法48只BALB／C小鼠按随机数字表法随机分为正常组、哮喘组、地塞米松组和Tubastatin A Hcl组各12只。测定各组小鼠气管反应性，计数其支气管肺泡灌洗液（BALF）中细胞总数和分类细胞数以及白细胞介素（IL）-4、IL-5和γ干扰素（IFN-γ）水平。取各组小鼠肺组织分别通过HE染色观察气管炎症浸润、AB-PAS染色观察气管上皮杯状细胞化生、Masson染色观察肺组织胶原沉积情况。结果Tubastatin A Hcl组气管反应性显著低于哮喘组[（4．18±0．94）比（6．02±0．47），P〈0．05]；Tubastatin A Hcl组BALF中炎症细胞总数[（57．0±5．7）×10^4／ml比（87．0±5．6）×10^4／m1]、嗜酸性粒细胞数[（6．8±1．7）×10^4／ml比（12．3±3．5）×10^4／m1]、IL-4[（19．3±2．7）比（26．2±3．2）ng／ml]水平均显著低于哮喘组（均P〈0．05），IL-5低于哮喘组、IFN-γ水平高于哮喘组但差异均无统计学意义（均P〉0．05）；Tubastatin A Hcl组肺组织气管血管周围炎症细胞浸润程度、炎症细胞数[（9．80±2．42）比（20．67±7．53）个]、炎症评分[（2．20±0．70）比（3．60±0．68）分]、杯状细胞化生百分比[（50．46±5．03）％比（71．06±5．38）％]均显著低于哮喘组（均P〈0．05），胶原沉积面积低于哮喘组但差异无统计学意义（P〉0．05）。但上述结果地塞米松组均略优于TubastatinAHcl组但差异均无统计学意义（均P〉0．05）。结论Tubastatin A Hcl能够有效缓解急性期哮喘气管炎症水平，但其抗炎作用有限，效果并不如地塞米松显著。
文摘Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed countries.Pancreatic cancer is difficult to diagnose,allowing few patients to have the necessary treatment at a relatively early stage.Despite a marginal benefit in survival,the overall response of pancreatic cancer to current systemic therapy continues to be poor,and new therapies are desperately needed.Histone deacetylase(HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors(HDACIs) have been shown to induce differentiation and cell cycle arrest,activate the extrinsic or intrinsic pathways of apoptosis,and inhibit invasion,migration and angiogenesis in different cancer cell lines.As a result of promising preclinical data,various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies.Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma.The use of HDACIs in clinical trials,in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed.Unfortunately,clinical data for HDACIs in patients with pancreatic cancer are inadequate,because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase Ⅱ/Ⅲ trials,among others with advanced solid tumors,is very limited.More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.
