PubMed:23633923 JSONTXT

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"23633923-0#46#49#gene10018","span":{"begin":46,"end":49},"obj":"gene10018"},{"id":"23633923-0#53#83#diseaseC0206180","span":{"begin":53,"end":83},"obj":"diseaseC0206180"},{"id":"23633923-2#68#71#gene238","span":{"begin":248,"end":251},"obj":"gene238"},{"id":"23633923-2#154#157#gene4869","span":{"begin":334,"end":337},"obj":"gene4869"},{"id":"23633923-2#73#103#diseaseC0206180","span":{"begin":253,"end":283},"obj":"diseaseC0206180"},{"id":"23633923-2#105#109#diseaseC0206180","span":{"begin":285,"end":289},"obj":"diseaseC0206180"},{"id":"23633923-2#158#167#diseaseC1332078","span":{"begin":338,"end":347},"obj":"diseaseC1332078"}],"relations":[{"id":"46#49#gene1001853#83#diseaseC0206180","pred":"associated_with","subj":"23633923-0#46#49#gene10018","obj":"23633923-0#53#83#diseaseC0206180"},{"id":"68#71#gene23873#103#diseaseC0206180","pred":"associated_with","subj":"23633923-2#68#71#gene238","obj":"23633923-2#73#103#diseaseC0206180"},{"id":"68#71#gene238105#109#diseaseC0206180","pred":"associated_with","subj":"23633923-2#68#71#gene238","obj":"23633923-2#105#109#diseaseC0206180"},{"id":"68#71#gene238158#167#diseaseC1332078","pred":"associated_with","subj":"23633923-2#68#71#gene238","obj":"23633923-2#158#167#diseaseC1332078"},{"id":"154#157#gene486973#103#diseaseC0206180","pred":"associated_with","subj":"23633923-2#154#157#gene4869","obj":"23633923-2#73#103#diseaseC0206180"},{"id":"154#157#gene4869105#109#diseaseC0206180","pred":"associated_with","subj":"23633923-2#154#157#gene4869","obj":"23633923-2#105#109#diseaseC0206180"},{"id":"154#157#gene4869158#167#diseaseC1332078","pred":"associated_with","subj":"23633923-2#154#157#gene4869","obj":"23633923-2#158#167#diseaseC1332078"}],"text":"Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex.\nBIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":46,"end":49},"obj":"gene:10018"},{"id":"T1","span":{"begin":53,"end":83},"obj":"disease:C0206180"},{"id":"T2","span":{"begin":248,"end":251},"obj":"gene:238"},{"id":"T3","span":{"begin":285,"end":289},"obj":"disease:C0206180"},{"id":"T4","span":{"begin":248,"end":251},"obj":"gene:238"},{"id":"T5","span":{"begin":253,"end":283},"obj":"disease:C0206180"},{"id":"T6","span":{"begin":231,"end":234},"obj":"gene:10018"},{"id":"T7","span":{"begin":253,"end":283},"obj":"disease:C0206180"},{"id":"T8","span":{"begin":334,"end":337},"obj":"gene:4869"},{"id":"T9","span":{"begin":253,"end":283},"obj":"disease:C0206180"},{"id":"T10","span":{"begin":334,"end":337},"obj":"gene:4869"},{"id":"T11","span":{"begin":285,"end":289},"obj":"disease:C0206180"},{"id":"T12","span":{"begin":338,"end":341},"obj":"gene:238"},{"id":"T13","span":{"begin":253,"end":283},"obj":"disease:C0206180"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex.\nBIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation."}

{"project":"Allie","denotations":[{"id":"SS1_23633923_2_0","span":{"begin":253,"end":283},"obj":"expanded"},{"id":"SS2_23633923_2_0","span":{"begin":285,"end":289},"obj":"abbr"}],"relations":[{"id":"AE1_23633923_2_0","pred":"abbreviatedTo","subj":"SS1_23633923_2_0","obj":"SS2_23633923_2_0"}],"text":"Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex.\nBIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":253,"end":283},"obj":"HP_0012193"},{"id":"T2","span":{"begin":275,"end":283},"obj":"HP_0002665"}],"text":"Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex.\nBIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation."}