The long-term effectiveness of targeted cancer therapies is limited by the development of resistance.Although epigenetic reprogramming has been implicated in resistance,the mechanisms remain elusive.Herein,we demonstr...The long-term effectiveness of targeted cancer therapies is limited by the development of resistance.Although epigenetic reprogramming has been implicated in resistance,the mechanisms remain elusive.Herein,we demonstrate that increased chromatin accessibility is involved in adaptive BRAF inhibitor(BRAFi)-resistance in melanoma cells.We observed loss of chromatin assembly factor 1(CAF-1)and its related histone H3 lysine 9 trimethylation(H3K9me3)with adaptive BRAFi resistance.We further showed that depletion of CAF-1 provides chromatin plasticity for effective reprogramming by AP1 components to promote BRAFi resistance.Our data sug-gest that therapeutic approaches to restore H3K9me3 levels may compensate for the loss of CAF-1 and,in turn,suppress resistance to BRAF inhibitors.展开更多
变应性鼻炎（AR）是一个全球性健康问题,全球发病率达10%～40%,且患者人数仍在增加,影响日常生活、工作及学习,造成经济上的沉重负担。为此2001年世界卫生组织参与制定了＂变应性鼻炎及其对哮喘的影响（allergic rhinitis and its impac...变应性鼻炎（AR）是一个全球性健康问题,全球发病率达10%～40%,且患者人数仍在增加,影响日常生活、工作及学习,造成经济上的沉重负担。为此2001年世界卫生组织参与制定了＂变应性鼻炎及其对哮喘的影响（allergic rhinitis and its impact on asthma,ARIA）＂指南,展开更多
基金supported by the National Institutes of Health to R.B.D.(NIH5P30CA015083)the Mayo Clinic Cancer Center Ea-gles Cancer Fund(Z.W.)the Mayo Clinic Center for Biomedical Discovery(S.M.O).
文摘The long-term effectiveness of targeted cancer therapies is limited by the development of resistance.Although epigenetic reprogramming has been implicated in resistance,the mechanisms remain elusive.Herein,we demonstrate that increased chromatin accessibility is involved in adaptive BRAF inhibitor(BRAFi)-resistance in melanoma cells.We observed loss of chromatin assembly factor 1(CAF-1)and its related histone H3 lysine 9 trimethylation(H3K9me3)with adaptive BRAFi resistance.We further showed that depletion of CAF-1 provides chromatin plasticity for effective reprogramming by AP1 components to promote BRAFi resistance.Our data sug-gest that therapeutic approaches to restore H3K9me3 levels may compensate for the loss of CAF-1 and,in turn,suppress resistance to BRAF inhibitors.
文摘变应性鼻炎（AR）是一个全球性健康问题,全球发病率达10%～40%,且患者人数仍在增加,影响日常生活、工作及学习,造成经济上的沉重负担。为此2001年世界卫生组织参与制定了＂变应性鼻炎及其对哮喘的影响（allergic rhinitis and its impact on asthma,ARIA）＂指南,
