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Protein & Cell Feb 2018Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic... (Review)
Review
Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.
Topics: Chromatin Assembly and Disassembly; DNA-Binding Proteins; Disease; Humans; Metabolism; Nutrients; Signal Transduction
PubMed: 28688083
DOI: 10.1007/s13238-017-0442-2 -
Biochemistry and Cell Biology =... Dec 2021Chromatin remodeling complexes alter chromatin structure to control access to DNA and therefore control cellular processes such as transcription, DNA replication, and...
Chromatin remodeling complexes alter chromatin structure to control access to DNA and therefore control cellular processes such as transcription, DNA replication, and DNA repair. CECR2 is a chromatin remodeling factor that plays an important role in neural tube closure and reproduction. Loss-of-function mutations in result primarily in perinatal lethal neural tube defect exencephaly, with non-penetrant mice that survive to adulthood exhibiting subfertility. CECR2 forms a complex with ISWI proteins SMARCA5 and (or) SMARCA1; however, further information on the structure and function of the complex is not known. Therefore, we identified candidate components of the CECR2-containing remodeling factor (CERF) complex in embryonic stem (ES) cells using mass spectroscopy. Both SMARCA5 and SMARCA1 were confirmed to be present in the CERF complexes in ES cells and testes. However, the novel proteins CCAR2 and LUZP1 are CERF components in ES cells, but not in the testis. This tissue specificity in mice suggests that these complexes may also have functional differences. Furthermore, LUZP1, the loss of which is also associated with exencephaly, appears to play a role in stabilizing the CERF complex in ES cells.
Topics: Adaptor Proteins, Signal Transducing; Animals; Chromatin; Chromatin Assembly and Disassembly; DNA Repair; DNA-Binding Proteins; Female; Male; Mice; Neural Tube Defects; Pregnancy; Transcription Factors
PubMed: 34197713
DOI: 10.1139/bcb-2021-0019 -
Cellular and Molecular Life Sciences :... Jul 2015Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and... (Review)
Review
Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure-function relationship studies which will be tackled best by an integrated biology approach.
Topics: Chromatin Assembly and Disassembly; DNA Methylation; DNA-Binding Proteins; Gene Expression Regulation; Histone Chaperones; Histone Deacetylases; Humans; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Models, Molecular; Protein Conformation
PubMed: 25796366
DOI: 10.1007/s00018-015-1880-8 -
Advanced Science (Weinheim,... Apr 2024Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells...
Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.
Topics: Colorectal Neoplasms; Humans; Chromatin Assembly and Disassembly; Mice; Animals; Organoids; Disease Models, Animal
PubMed: 38380561
DOI: 10.1002/advs.202303379 -
Cell Aug 2013Chromatin provides both a means to accommodate a large amount of genetic material in a small space and a means to package the same genetic material in different... (Review)
Review
Chromatin provides both a means to accommodate a large amount of genetic material in a small space and a means to package the same genetic material in different chromatin states. Transitions between chromatin states are enabled by chromatin-remodeling ATPases, which catalyze a diverse range of structural transformations. Biochemical evidence over the last two decades suggests that chromatin-remodeling activities may have emerged by adaptation of ancient DNA translocases to respond to specific features of chromatin. Here, we discuss such evidence and also relate mechanistic insights to our understanding of how chromatin-remodeling enzymes enable different in vivo processes.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Chromatin Assembly and Disassembly; DNA; Eukaryota; Humans; Nucleosomes; Transferases
PubMed: 23911317
DOI: 10.1016/j.cell.2013.07.011 -
Cellular and Molecular Gastroenterology... 2019
Topics: Animals; Carcinogenesis; Chromatin Assembly and Disassembly; Female; Inflammation; Mice; Proto-Oncogene Proteins p21(ras); X-linked Nuclear Protein
PubMed: 30539789
DOI: 10.1016/j.jcmgh.2018.10.001 -
Frontiers in Bioscience (Landmark... Jan 2012In order to maintain chromosomal stability during cell division, eukaryotic cells have evolved a number of surveillance mechanisms termed checkpoints. These checkpoints... (Review)
Review
In order to maintain chromosomal stability during cell division, eukaryotic cells have evolved a number of surveillance mechanisms termed checkpoints. These checkpoints monitor the completion of essential molecular and cellular processes of one stage before entering another. The spindle checkpoint watches the bi-orientation attachment of spindle microtubules to all condensed chromosomes before initiation of nuclear division during mitosis. Histones are subject to a number of post-translational modifications during the cell cycle, which may in turn modify or facilitate cell cycle progression. Recent studies suggest that mitotic proteins including Bub1 and Sgo1 that are involved in the spindle checkpoint also play a major role in the regulation of histone modifications and chromatin remodeling. This mini-review summarizes emerging information about the new role of spindle checkpoint proteins in chromatin remodeling.
Topics: Animals; Cell Cycle Proteins; Chromatin Assembly and Disassembly; Humans; M Phase Cell Cycle Checkpoints; Models, Biological; Protein Isoforms; Protein Serine-Threonine Kinases
PubMed: 22201785
DOI: 10.2741/3968 -
Oncotarget May 2016
Topics: Chromatin; Chromatin Assembly and Disassembly; Humans; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor Receptor-2
PubMed: 27127877
DOI: 10.18632/oncotarget.7922 -
Nature Communications Nov 2022The assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other...
The assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other components through proteolysis, causing cancers. Here, we show that mouse Lsd1/Kdm1a deletion causes dramatic dissolution of SWI/SNF complexes and that LSD1 demethylates the methylated lysine residues in SMARCC1 and SMARCC2 to preserve the structural integrity of SWI/SNF complexes. The methylated SMARCC1/SMARCC2 are targeted for proteolysis by L3MBTL3 and the CRL4 ubiquitin ligase complex. We identify SMARCC1 as the critical target of LSD1 and L3MBTL3 to maintain the pluripotency and self-renewal of embryonic stem cells. L3MBTL3 also regulates SMARCC1/SMARCC2 proteolysis induced by the loss of SWI/SNF subunits. Consistently, mouse L3mbtl3 deletion causes striking accumulation of SWI/SNF components, associated with embryonic lethality. Our studies reveal that the assembly/disassembly of SWI/SNF complexes is dynamically controlled by a lysine-methylation dependent proteolytic mechanism to maintain the integrity of the SWI/SNF complexes.
Topics: Mice; Animals; Chromatin Assembly and Disassembly; Methylation; Lysine; Proteolysis; Chromatin; Histone Demethylases; Mammals
PubMed: 36335117
DOI: 10.1038/s41467-022-34348-9 -
International Journal of Molecular... Feb 2021Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration,... (Review)
Review
Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are epigenetically regulated and are required for stress-induced transcriptional regulation or reprogramming. Epigenetic regulators facilitate the phenotypic plasticity of development and the survival and reproduction of plants in unfavorable environments, and they are highly diversified, including histone and DNA modifiers, histone variants, chromatin remodelers, and regulatory non-coding RNAs. They contribute to chromatin modifications, remodeling and dynamics, and constitute a multilayered and multifaceted circuitry for sophisticated and robust epigenetic regulation of plant stress responses. However, this complicated epigenetic regulatory circuitry creates challenges for elucidating the common or differential roles of chromatin modifications for transcriptional regulation or reprogramming in different plant stress responses. Particularly, interacting chromatin modifications and heritable stress memories are difficult to identify in the aspect of chromatin-based epigenetic regulation of transcriptional reprogramming and memory. Therefore, this review discusses the recent updates from the three perspectives-stress specificity or dependence of transcriptional reprogramming, the interplay of chromatin modifications, and transcriptional stress memory in plants. This helps solidify our knowledge on chromatin-based transcriptional reprogramming for plant stress response and memory.
Topics: Adaptation, Physiological; Chromatin; Chromatin Assembly and Disassembly; Droughts; Epigenesis, Genetic; Gene Expression Regulation, Plant; Plants; Salinity; Stress, Physiological; Temperature
PubMed: 33670556
DOI: 10.3390/ijms22042013