Michael S Torok, Marilyn G Pray-Grant, Benjamin M Grant, Meagan E Josephs, Patrick A Grant
The post-translational acetylation of the histone components of chromatin mediates numerous DNA-templated events, including transcriptional activation, DNA repair, and genomic replication. The conserved SAGA (Spt-Ada-Gcn5 Acetyltranferase) and SLIK (SAGA-Like) Histone Acetyltransferase (HAT) complexes are required for transcriptional activation of a subset of yeast genes and contain multiple subunits including the histone fold-containing TBP- Associated Factors (TAFs): 6, 9, 10, and 12. These TAFs are also components of the TFIID complex and are consequently involved in most RNA polymerase II-transcription in yeast. Here we identify a novel conserved region of TAF12, termed ReNu, outside of its histone fold, which is required for SAGA and SLIK-directed nucleosomal acetylation. We demonstrate that this region is not required for chromatin association, but show that this region plays an important role for histone H3 acetylation at specific SAGA and SLIK-regulated promoters. Our data suggests that the ReNu region of TAF12 regulates Gcn5 acetylation of specific substrates within the SAGA super-family of HAT complexes.
{"title":"The Novel ReNu Region of TAF12 Regulates Gcn5 Nucleosomal Acetylation.","authors":"Michael S Torok, Marilyn G Pray-Grant, Benjamin M Grant, Meagan E Josephs, Patrick A Grant","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The post-translational acetylation of the histone components of chromatin mediates numerous DNA-templated events, including transcriptional activation, DNA repair, and genomic replication. The conserved SAGA (Spt-Ada-Gcn5 Acetyltranferase) and SLIK (SAGA-Like) Histone Acetyltransferase (HAT) complexes are required for transcriptional activation of a subset of yeast genes and contain multiple subunits including the histone fold-containing TBP- Associated Factors (TAFs): 6, 9, 10, and 12. These TAFs are also components of the TFIID complex and are consequently involved in most RNA polymerase II-transcription in yeast. Here we identify a novel conserved region of TAF12, termed ReNu, outside of its histone fold, which is required for SAGA and SLIK-directed nucleosomal acetylation. We demonstrate that this region is not required for chromatin association, but show that this region plays an important role for histone H3 acetylation at specific SAGA and SLIK-regulated promoters. Our data suggests that the ReNu region of TAF12 regulates Gcn5 acetylation of specific substrates within the SAGA super-family of HAT complexes.</p>","PeriodicalId":92672,"journal":{"name":"Journal of molecular genetics (Isleworth, London, England)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437354/pdf/nihms-1616406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38295533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-01Epub Date: 2018-04-01DOI: 10.31038/JMG.1000101
Marwa El-Deeb, Patrick Adams, Andrea Schneider, Maria J Salcedo-Arellano, Flora Tassone, Randi Hagerman
Fragile X-associated tremor/ataxia syndrome (FXTAS) affects individuals with 55-200 CGG repeats (premutation) in the 5'-untranslated region of the fragile X mental retardation 1 (FMR1) gene. FXTAS is a progressive neurodegenerative disorder associated with an action tremor, cerebellar ataxia memory and executive function deficits, autonomic dysfunction and neuropathy. Females with the fragile X premutation are often affected by fragile X-associated primary ovarian insufficiency (FXPOI), and may have other medical conditions such as fibromyalgia, depression, anxiety, and immune-mediated disorders like hypothyroidism. Here we present a case of a 54-year-old woman with tremor, ataxia, average memory skills, and executive function deficits who meets criteria for FXTAS. She also has anxiety, Major Depressive Disorder, fibromyalgia, chronic pain and was treated chronically with opioids and she overdosed on fentanyl leading to significant CNS dysfunction.
{"title":"Fentanyl overdose in a female with the <i>FMR1</i> premutation and FXTAS.","authors":"Marwa El-Deeb, Patrick Adams, Andrea Schneider, Maria J Salcedo-Arellano, Flora Tassone, Randi Hagerman","doi":"10.31038/JMG.1000101","DOIUrl":"https://doi.org/10.31038/JMG.1000101","url":null,"abstract":"<p><p>Fragile X-associated tremor/ataxia syndrome (FXTAS) affects individuals with 55-200 CGG repeats (premutation) in the 5'-untranslated region of the <i>fragile X mental retardation 1 (FMR1)</i> gene. FXTAS is a progressive neurodegenerative disorder associated with an action tremor, cerebellar ataxia memory and executive function deficits, autonomic dysfunction and neuropathy. Females with the fragile X premutation are often affected by fragile X-associated primary ovarian insufficiency (FXPOI), and may have other medical conditions such as fibromyalgia, depression, anxiety, and immune-mediated disorders like hypothyroidism. Here we present a case of a 54-year-old woman with tremor, ataxia, average memory skills, and executive function deficits who meets criteria for FXTAS. She also has anxiety, Major Depressive Disorder, fibromyalgia, chronic pain and was treated chronically with opioids and she overdosed on fentanyl leading to significant CNS dysfunction.</p>","PeriodicalId":92672,"journal":{"name":"Journal of molecular genetics (Isleworth, London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482838/pdf/nihms-1018920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37194337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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