11,867 results match your criteria remodeling chromatin

H3.3 kinetics predicts chromatin compaction status of parental genomes in early embryos.

Reprod Biol Endocrinol 2021 Jun 11;19(1):87. Epub 2021 Jun 11.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.

Background: After fertilization, the fusion of gametes results in the formation of totipotent zygote. During sperm-egg fusion, maternal factors participate in parental chromatin remodeling. H3. Read More

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Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes.

PLoS One 2021 11;16(6):e0252895. Epub 2021 Jun 11.

Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, Kingsville, Texas, United States of America.

Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity. Read More

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The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation.

Nat Commun 2021 06 10;12(1):3520. Epub 2021 Jun 10.

Epigenetics Section, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA.

The Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is caused by mutations in LSH/HELLS, a chromatin remodeler promoting incorporation of histone variant macroH2A. Here, we demonstrate that LSH depletion results in degradation of nascent DNA at stalled replication forks and the generation of genomic instability. The protection of stalled forks is mediated by macroH2A, whose knockdown mimics LSH depletion and whose overexpression rescues nascent DNA degradation. Read More

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Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis.

Cell Oncol (Dordr) 2021 Jun 9. Epub 2021 Jun 9.

Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, 59 Haier Road, Shandong, 266000, Qingdao, China.

Background: ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. Read More

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The Bidirectional Relationship Between Cancer Epigenetics and Metabolism.

Annu Rev Cancer Biol 2021 Mar 30;5(1):235-257. Epub 2020 Nov 30.

Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Metabolic and epigenetic reprogramming are characteristics of cancer cells that, in many cases, are linked. Oncogenic signaling, diet, and tumor microenvironment each influence the availability of metabolites that are substrates or inhibitors of epigenetic enzymes. Reciprocally, altered expression or activity of chromatin-modifying enzymes can exert direct and indirect effects on cellular metabolism. Read More

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High Resolution View on the Regulation of Recombinase Accumulation in Mammalian Meiosis.

Front Cell Dev Biol 2021 24;9:672191. Epub 2021 May 24.

Department of Developmental Biology, Erasmus MC, Rotterdam, Netherlands.

A distinguishing feature of meiotic DNA double-strand breaks (DSBs), compared to DSBs in somatic cells, is the fact that they are induced in a programmed and specifically orchestrated manner, which includes chromatin remodeling prior to DSB induction. In addition, the meiotic homologous recombination (HR) repair process that follows, is different from HR repair of accidental DSBs in somatic cells. For instance, meiotic HR involves preferred use of the homolog instead of the sister chromatid as a repair template and subsequent formation of crossovers and non-crossovers in a tightly regulated manner. Read More

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Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex.

Immunity 2021 Jun 2. Epub 2021 Jun 2.

Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

Microbe-derived acetate activates the Drosophila immunodeficiency (IMD) pathway in a subset of enteroendocrine cells (EECs) of the anterior midgut. In these cells, the IMD pathway co-regulates expression of antimicrobial and enteroendocrine peptides including tachykinin, a repressor of intestinal lipid synthesis. To determine whether acetate acts on a cell surface pattern recognition receptor or an intracellular target, we asked whether acetate import was essential for IMD signaling. Read More

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GCN5 enables HSP12 induction promoting chromatin remodeling not histone acetylation.

Biochem Cell Biol 2021 Jun 8. Epub 2021 Jun 8.

Università degli Studi di Roma La Sapienza, 9311, Dipartimento di Biologia e Biotecnologie, Piazzale A. Moro 5, Roma, Italy, 00185;

Regulation of stress responsive genes represents one of the best examples of gene induction and the relevance and involvement of different regulators may change for a given gene depending on the challenging stimulus. HSP12 gene is induced by very different stimuli, however the molecular response to the stress has been characterized in detail only for heat shock treatments. In this work we want to verify whether, the regulation of transcription induced by oxidative stress, utilizes the same epigenetic solutions relative to those employed in heat shock response. Read More

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Three-dimensional folding dynamics of the Xenopus tropicalis genome.

Nat Genet 2021 Jun 7. Epub 2021 Jun 7.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Animal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. Read More

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Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples.

J Vis Exp 2021 May 21(171). Epub 2021 May 21.

Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL); Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory (EMBL), University of Heidelberg; Dept. of Chemical Physiology and Biochemistry, Oregon Health and Science University;

Proteases are regulators of countless physiological processes and the precise investigation of their activities remains an intriguing biomedical challenge. Among the ~600 proteases encoded by the human genome, neutrophil serine proteases (NSPs) are thoroughly investigated for their involvement in the onset and progression of inflammatory conditions including respiratory diseases. Uniquely, secreted NSPs not only diffuse within extracellular fluids but also localize to plasma membranes. Read More

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AP-1 is a temporally regulated dual gatekeeper of reprogramming to pluripotency.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305;

Somatic cell transcription factors are critical to maintaining cellular identity and constitute a barrier to human somatic cell reprogramming; yet a comprehensive understanding of the mechanism of action is lacking. To gain insight, we examined epigenome remodeling at the onset of human nuclear reprogramming by profiling human fibroblasts after fusion with murine embryonic stem cells (ESCs). By assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and chromatin immunoprecipitation sequencing we identified enrichment for the activator protein 1 (AP-1) transcription factor c-Jun at regions of early transient accessibility at fibroblast-specific enhancers. Read More

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The BAFfling story of MN1-induced leukemogenesis.

Mol Cell 2021 Jun;81(11):2268-2269

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Molecular Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. Electronic address:

Riedel et al. (2021) show that expression of MN1 is capable of blocking myeloid differentiation and initiating leukemia through mechanisms that require Brg1-containing chromatin remodeling complexes. Intriguingly, this process depends on an unstructured polyglutamine repeat region within MN1. Read More

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Nuclear Sphingosine-1-phosphate Lyase Generated ∆2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells.

Cell Biochem Biophys 2021 Jun 3. Epub 2021 Jun 3.

Departments of Pharmacology & Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, is generated from sphingosine by sphingosine kinases (SPHKs) 1 and 2 and is metabolized to ∆2-hexadecenal (∆2-HDE) and ethanolamine phosphate by S1P lyase (S1PL) in mammalian cells. We have recently demonstrated the activation of nuclear SPHK2 and the generation of S1P in the nucleus of lung epithelial cells exposed to Pseudomonas aeruginosa. Here, we have investigated the nuclear localization of S1PL and the role of ∆2-HDE generated from S1P in the nucleus as a modulator of histone deacetylase (HDAC) activity and histone acetylation. Read More

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Targeting glutamine dependence through GLS1 inhibition suppresses ARID1A-inactivated clear cell ovarian carcinoma.

Nat Cancer 2021 Feb 11;2(2):189-200. Epub 2021 Jan 11.

Immunology, Microenvironment & Metastasis Program, The Wistar Institute, Philadelphia, PA, USA.

Alterations in components of the SWI/SNF chromatin-remodeling complex occur in ~20% of all human cancers. For example, is mutated in up to 62% of clear cell ovarian carcinoma (OCCC), a disease currently lacking effective therapies. Here we show that mutation creates a dependence on glutamine metabolism. Read More

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February 2021

Role and potential clinical utility of ARID1A in gastrointestinal malignancy.

Mutat Res 2021 Jan-Jun;787:108360. Epub 2020 Dec 4.

Program of Food Science and Technology, Division of Science and Technology, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, 519085, Guangdong Province, China. Electronic address:

ARID1A (AT-rich interactive domain 1A) is a newly discovered tumor suppressor gene, and its encoded product is an important component of the SWI/SNF chromatin remodeling complex. ARID1A plays an important role in cell proliferation, invasion and metastasis, apoptosis, cell cycle regulation, epithelial mesenchymal transition, and the regulation of other of biological behaviors. Recently, ARID1A mutations have been increasingly reported in esophageal adenocarcinoma, gastric cancer, colorectal cancer, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, and other malignant tumors of the digestive system. Read More

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December 2020

Interplay between DNA replication stress, chromatin dynamics and DNA-damage response for the maintenance of genome stability.

Mutat Res 2021 Jan-Jun;787:108346. Epub 2020 Nov 27.

University Medical Center Hamburg-Eppendorf, Department of Radiotherapy, Laboratory of Radiobiology & Experimental Radiation Oncology, Germany. Electronic address:

DNA replication stress is a major source of DNA damage, including double-stranded breaks that promote DNA damage response (DDR) signaling. Inefficient repair of such lesions can affect genome integrity. During DNA replication different factors act on chromatin remodeling in a coordinated way. Read More

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November 2020

The role of demethylases in cardiac development and disease.

J Mol Cell Cardiol 2021 May 31;158:89-100. Epub 2021 May 31.

Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, United States of America; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States of America. Electronic address:

Heart failure is a worldwide health condition that currently has limited noninvasive treatments. Heart disease includes both structural and molecular remodeling of the heart which is driven by alterations in gene expression in the cardiomyocyte. Therefore, understanding the regulatory mechanisms which instigate these changes in gene expression and constitute the foundation for pathological remodeling may be beneficial for developing new treatments for heart disease. Read More

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Dioscin elevates lncRNA MANTIS in therapeutic angiogenesis for heart diseases.

Aging Cell 2021 Jun 3:e13392. Epub 2021 Jun 3.

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.

Dioscin has been widely used in clinics for coronary artery disease (CAD) treatment for years in China. However, the underlying mechanism for Dioscin-mediated cardioprotective effect has not been elucidated. Here, we showed that Dioscin significantly rescues the cardiac function in mouse model of myocardial infarction (MI), accompanied by the reduction of cardiac fibrosis and apoptosis, resulting from elevated angiogenesis. Read More

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A Glimpse into the Structural Properties of the Intermediate and Transition State in the Folding of Bromodomain 2 Domain 2 by Φ Value Analysis.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza University of Rome, 00185 Rome, Italy.

Bromodomains (BRDs) are small protein interaction modules of about 110 amino acids that selectively recognize acetylated lysine in histones and other proteins. These domains have been identified in a variety of multi-domain proteins involved in transcriptional regulation or chromatin remodeling in eukaryotic cells. BRD inhibition is considered an attractive therapeutic approach in epigenetic disorders, particularly in oncology. Read More

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O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair.

Int J Mol Sci 2021 May 27;22(11). Epub 2021 May 27.

Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung GmbH, 64291 Darmstadt, Germany.

Exposing cells to DNA damaging agents, such as ionizing radiation (IR) or cytotoxic chemicals, can cause DNA double-strand breaks (DSBs), which are crucial to repair to maintain genetic integrity. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification (PTM), which has been reported to be involved in the DNA damage response (DDR) and chromatin remodeling. Here, we investigated the impact of O-GlcNAcylation on the DDR, DSB repair and chromatin status in more detail. Read More

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Global Chromatin Changes Resulting from Single-Gene Inactivation-The Role of SMARCB1 in Malignant Rhabdoid Tumor.

Cancers (Basel) 2021 May 23;13(11). Epub 2021 May 23.

School of Medicine, Trinity College, University of Dublin, Dublin 2, Ireland.

Human cancer typically results from the stochastic accumulation of multiple oncogene-activating and tumor-suppressor gene-inactivating mutations. However, this process takes time and especially in the context of certain pediatric cancer, fewer but more 'impactful' mutations may in short order produce the full-blown cancer phenotype. This is well exemplified by the highly aggressive malignant rhabdoid tumor (MRT), where the only gene classically showing recurrent inactivation is SMARCB1, a subunit member of the BAF chromatin-remodeling complex. Read More

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Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer.

Cedric R Clapier

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Department of Oncological Sciences & Howard Hughes Medical Institute, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.

The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions-in particular, the regulation of gene expression-and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. Read More

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Peculiarities of Gene Regulation and Chromatin Structure.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Department of Biochemistry, Genetics and Microbiology, Biochemistry III, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.

The highly complex life cycle of the human malaria parasite, , is based on an orchestrated and tightly regulated gene expression program. In general, eukaryotic transcription regulation is determined by a combination of sequence-specific transcription factors binding to regulatory DNA elements and the packaging of DNA into chromatin as an additional layer. The accessibility of regulatory DNA elements is controlled by the nucleosome occupancy and changes of their positions by an active process called nucleosome remodeling. Read More

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Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling.

Int J Mol Sci 2021 May 6;22(9). Epub 2021 May 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd's expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. Read More

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Do Transgenerational Epigenetic Inheritance and Immune System Development Share Common Epigenetic Processes?

J Dev Biol 2021 May 12;9(2). Epub 2021 May 12.

Active Motif, Incorporated, 1914 Palomar Oaks Way, Suite 150, Carlsbad, CA 92008, USA.

Epigenetic modifications regulate gene expression for development, immune response, disease, and other processes. A major role of epigenetics is to control the dynamics of chromatin structure, i.e. Read More

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α-Synuclein A53T Binds to Transcriptional Adapter 2-Alpha and Blocks Histone H3 Acetylation.

Int J Mol Sci 2021 May 20;22(10). Epub 2021 May 20.

Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.

α-Synuclein (α-syn) is a hallmark amyloidogenic protein component of Lewy bodies in dopaminergic neurons affected by Parkinson's disease (PD). Despite the multi-faceted gene regulation of α-syn in the nucleus, the mechanism underlying α-syn crosstalk in chromatin remodeling in PD pathogenesis remains elusive. Here, we identified transcriptional adapter 2-alpha (TADA2a) as a novel binding partner of α-syn using the BioID system. Read More

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Expression of Immuno-Oncologic Biomarkers Is Enriched in Colorectal Cancers and Other Solid Tumors Harboring the A59T Variant of .

Cells 2021 May 21;10(6). Epub 2021 May 21.

Caris Life Sciences, Phoenix, AZ 85040, USA.

The molecular heterogeneity of is well established, with a pool of variants comprising >75% of all known mutations; this pool includes mutations in classic codons 12, 13, and 61, as well as 146 and 117. In addition, there are rare variants that are more frequently encountered clinically due to the advances in next-generation sequencing and more widespread implementation of All- sequencing over the past five years. We have previously identified a missense variant of , A59T, in a patient with CRC that was associated with a response to an epidermal growth factor inhibitor when added to chemotherapy, supporting the hypothesis that distinct biochemical impacts of different mutations may produce varied responses to targeted therapy. Read More

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The Multiple Facets of ATRX Protein.

Cancers (Basel) 2021 May 5;13(9). Epub 2021 May 5.

Department of Science, University Roma Tre, 00146 Rome, Italy.

ATRX gene codifies for a protein member of the SWI-SNF family and was cloned for the first time over 25 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability called Alpha Thalassemia/mental Retardation syndrome X-linked (ATRX) syndrome. Since its discovery as a helicase involved in alpha-globin gene transcriptional regulation, our understanding of the multiple roles played by the ATRX protein increased continuously, leading to the recognition of this multifaceted protein as a central "caretaker" of the human genome involved in cancer suppression. In this review, we report recent advances in the comprehension of the ATRX manifold functions that encompass heterochromatin epigenetic regulation and maintenance, telomere function, replicative stress response, genome stability, and the suppression of endogenous transposable elements and exogenous viral genomes. Read More

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Identification and characterization of Poly(ADP-ribose) polymerase-1 interacting proteins during development of Dictyostelium discoideum.

Protein Expr Purif 2021 May 29;186:105923. Epub 2021 May 29.

Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India. Electronic address:

Poly (ADP-ribose) polymerase-1 (PARP-1) is a multifunctional protein that is associated with various biological processes like chromatin remodeling, DNA damage, cell death etc. In Dictyostelium discoideum, PARP-1 has also been implicated in cellular differentiation and development. However, its interacting proteins during multicellular development are not yet explored. Read More

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Steroid receptor-coregulator transcriptional complexes: new insights from CryoEM.

Essays Biochem 2021 Jun 1. Epub 2021 Jun 1.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.

Steroid receptors activate gene transcription through recruitment of a number of coregulators to facilitate histone modification, chromatin remodeling, and general transcription machinery stabilization. Understanding the structures of full-length steroid receptor and coregulatory complexes has been difficult due to their large molecular sizes and dynamic structural conformations. Recent developments in cryo-electron microscopy (cryoEM) technology and proteomics have advanced the structural studies of steroid receptor complexes. Read More

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