A5017462551- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Galectins and Cancer Biology
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Plant Molecular Biology Research
- ATP Synthase and ATPases Research
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Developmental Biology and Gene Regulation
- Genomics, phytochemicals, and oxidative stress
- Sirtuins and Resveratrol in Medicine
- Protein Degradation and Inhibitors
- Cholinesterase and Neurodegenerative Diseases
- Insect Resistance and Genetics
- FOXO transcription factor regulation
- Cannabis and Cannabinoid Research
- Autophagy in Disease and Therapy
- Chemical Synthesis and Analysis
Wayne State University
2015-2025
The Barbara Ann Karmanos Cancer Institute
2015
National Institutes of Health
2000-2003
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2000-2001
University of Cincinnati Medical Center
2000
Regulation of gene expression by histone-modifying enzymes is essential to control cell fate decisions and developmental processes. Two enzymes, RPD3, a deacetylase, dKDM5/LID, demethylase, are present in single complex, coordinated through the SIN3 scaffold protein. While complex has been demonstrated have functional histone deacetylase activity, role demethylase dKDM5/LID as part not investigated. Here, we analyzed transcriptional activities relation SIN3. Knockdown either Sin3A or lid...
Epigenetic regulation and metabolism are connected. regulators, like the SIN3 complex, affect expression of a wide range genes, including those encoding metabolic enzymes essential for central carbon metabolism. The idea that epigenetic modifiers can sense respond to flux by regulating gene has long been proposed. In support this cross-talk, we provide data linking regulatory action on subset genes with cellular response changes in flux. Furthermore, show loss is linked decreases...
The SIN3 corepressor and RPD3 histone deacetylase are components of the evolutionarily conserved SIN3/RPD3 transcriptional repression complex. Here we show that complex SMRTER required for Drosophila G2 phase cell cycle progression. Loss SIN3, but not p55, SAP18, or SAP30, component by RNA interference (RNAi) causes a delay prior to initiation mitosis. reduces growth rate cells does cause distinct defect, suggesting delayed in multiple phases cycle, including G2. Thus, role progression...
The SIN3 corepressor serves as a scaffold for the assembly of histone deacetylase (HDAC) complexes. and its associated HDAC have been shown to critical roles in both development regulation cell cycle progression. Although multiple isoforms reported simple complex eukaryotic organisms, mechanisms by which such regulate specific biological processes are still largely uncharacterized. To gain insight into how isoform-specific function contributes growth metazoan organism, we affinity-purified...
Chromatin modification and cellular metabolism are tightly connected. modifiers regulate the expression of genes involved in and, turn, levels metabolites. The generated metabolites utilized by chromatin to affect epigenetic modification. mechanism for this cross-talk, however, remains incompletely understood. corepressor SIN3 controls histone acetylation through association with deacetylase RPD3. complex is known a number metabolic processes. Here, we find that Drosophila binds promoter...
Abstract Aberrant expression of the Forkhead box transcription factor, FOXQ1, is a prevalent mechanism epithelial-mesenchymal transition (EMT) and metastasis in multiple carcinoma types. However, it remains unknown how FOXQ1 regulates gene expression. Here, we report that initiates EMT by recruiting MLL/KMT2 histone methyltransferase complex as transcriptional coactivator. We first establish promoter recognition precedes MLL assembly histone-3 lysine-4 trimethylation within regions critical...
Coordinate control of gene activity is critical for fitness and longevity an organism. The SIN3 histone deacetylase (HDAC) complex functions as a transcriptional repressor many genes. SIN3-regulated genes include those that encode proteins affecting multiple aspects mitochondrial function, such energy production stress responsiveness, important health maintenance. Here we used Drosophila melanogaster model organism to examine the role in regulation longevity. Adult flies with RNA...
The multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, single Sin3A gene encodes different isoforms of SIN3, which 187 and 220 are the major isoforms. Previous studies have demonstrated functional non-redundancy role in regulating distinct biological processes, however, not well characterized. We established Drosophila S2 cell culture model system cells predominantly express either or 220. To identify genomic targets isoforms, we performed chromatin...
The TFIID transcription initiation complex is composed of TBP and multiple TAFs. Studies in unicellular systems indicate that TAF250 required for progression through G 1 /S the cell cycle repression apoptosis. Here we extend these vivo studies by determining developmental requirements a multicellular organism, Drosophila . mutants were isolated genetic screen also yielded TAF60 TAF110 mutants, indicating TAFs function coordinately to regulate transcription. Null alleles are recessive larval...
Abstract SIN3 is a component of histone deacetylase complex known to be important for transcription repression. While multiple isoforms have been reported, little about their relative expression or role in development. Using combination techniques, we determined that expressed throughout the Drosophila life cycle. The pattern each individual isoform, however, distinct. Knock down all reveals requirement this protein embryonic and larval periods. Taken together, data suggest required...
Abstract Background SIN3 is a transcriptional repressor protein known to regulate many genes, including number of those that encode mitochondrial components. Results By monitoring RNA levels, we find loss in Drosophila cultured cells results up-regulation not only nuclear encoded but also by the genome. The gene expression accompanied perturbation ATP levels SIN3-deficient cells, suggesting changes result altered activity. In support hypothesis necessary for normal function, yeast sin3 null...
DNA methylation in Drosophila melanogaster is restricted temporally during development and occurs at a significantly lower frequency than mammals. Thus, the regulatory functions, if any, of this form modification are unclear. However, presence homologs vertebrate methyl‐CpG‐binding proteins implies functional consequences for flies. This work describes properties dMBD‐like, homolog MBD2 MBD3. dMBD‐like dMBD‐likeδ (a splice variant) failed to bind model methylated probes, inconsistent with...
Histone methylation levels, which are determined by the action of both histone demethylases and methyltransferases, impact multiple biological processes affecting gene expression activity. Methionine metabolism generates major methyl donor S-adenosylmethionine (SAM) for methylation. The functions methionine metabolic enzymes in regulating as well interaction between pathway methylation, however, still not fully understood. Here, we report that reduced levels some involved lead to lethality...
Pleiotropically acting eukaryotic corepressors such as retinoblastoma and SIN3 have been found to physically interact with many widely expressed "housekeeping" genes. Evidence suggests that their roles at these loci are not provide binary on/off switches, is observed highly cell-type specific genes, but rather serve governors, directly modulating expression within certain bounds, while shutting down gene expression. This sort of regulation challenging study, the differential levels can be...
Abstract Establishment and maintenance of histone acetylation levels are critical for metazoan development viability. Disruption the balance between deacetylation by treatment with chemical deacetylase (HDAC) inhibitors results in loss cell proliferation, differentiation and/or apoptosis. Histone SIN3 complex is essential Drosophila mice, as scaffolding factor or associated HDAC lethality. The objective this study to elucidate contributions components these processes. We used model organism...