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The Parasite's Way of Life
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Once signaling pathways have been initiated, they often result in epigenetic changes that up or down-regulate specific genes. Epigenetics refers to heritable changes in phenotype or gene expression caused by mechanisms other than an alteration in the DNA sequence (see Box 2.4). One epigenetic phenomenon that appears to play a key role in parasite developmental change is the modification of chromatin structure. Chromatin refers to the complex of DNA and protein found in the cells of eukaryotes. By wrapping around these proteins, DNA is packaged into a more compact form, which prevents the DNA strands from becoming tangled. The characteristic shapes of chromosomes visible during mitosis are the result of DNA being coiled into highly condensed networks of chromatin.
Diagnosis and Pathobiology
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
About 50% of human cancers have mutations in chromatin proteins [283]. Approximately 6 billion coding and noncoding DNA bases are swaddled around ~30 million nucleosomes assembling an enormous, delicate, and intricately controlled macromolecular complex called ‘chromatin' [283]. The two major regions of chromatin include euchromatin (active genes containing an area with a relatively open configuration), and heterochromatin (late to replicate and highly condensed inactive gene containing area) [302]. Heterochromatin can be further separated into facultative heterochromatin, which encompasses repressed genes in a cell type-specific manner, and constitutive heterochromatin, which mainly encompasses repetitive sequences and transposons positioned at constant areas in different types of cells (e.g., pericentromeric regions) that can be transcribed at minute levels [323]. DNA and histone protein modifications, histone variants, components reading such modifications, noncoding RNAs, chromatin architectural proteins, and components remodeling chromatin, among others, are responsible for regulating the formation and maintenance of heterochromatin [323].
Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
Epigenetic regulation of gene expression is briefly introduced in Chapter 3 and a full chapter in this textbook is dedicated to epigenetics of exercise (Chapter 6), but given the importance of chromatin remodelling and modulation of DNA methylation as part of the signal transduction model, we will briefly cover the topic in this chapter too. The DNA in the human genome has been estimated to be almost 2 m long. In order to fit into a tiny nucleus of only 10 micrometres, it must be very tightly packaged. This DNA packaging is achieved by wrapping DNA around complexes which are built from eight histone proteins. DNA together with histone complexes is termed chromatin and the DNA wrapped around one histone complex is called a nucleosome.
Epigenetic control of skin immunity
Published in Immunological Medicine, 2023
Human cells contain two meters of genomic DNA that is tightly folded and packed within the nucleus. Genomic DNA forms a secondary structure referred to as chromatin that fits into a limited space [7]. The basic unit of chromatin, the nucleosome, is consisted of 147 bp genomic DNA and a core histone octamer. DNA is negatively charged and histones are positively charged, and the opposing charges allow DNA to wrap itself tightly around the histone octamer to form a nucleosome. Initiation of transcription requires the binding of RNA polymerase II and several basic transcription factors, called TFIIA and TFIIB, bind to promoters located near the transcription start sites [8]. Sequence-specific DNA-binding transcription factors (TFs) are involved in the enhancement of transcription. TFs bind to enhancers and cause genomic DNA to form looped structures that shorten the distance between enhancers and promoters, thereby promoting the transcription of the target genes. Transcriptional activity is also closely related to the degree of DNA condensation associated with chromatin structure [6,8]. Tightly packed chromatin, called closed chromatin or heterochromatin, restricts the access of RNA polymerase II and the transcription factors to the regulatory sites, and consequently, suppresses the expression of target genes. Open chromatin or euchromatin that is less condensed allows easier access of the transcriptional machinery to DNA, thus setting target genes to be more actively transcribed.
Phosphorus containing analogues of SAHA as inhibitors of HDACs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Michael D. Pun, Hsin-Hua Wu, Feyisola P. Olatunji, Britany N. Kesic, John W. Peters, Clifford E. Berkman
Chromatin is a protein–DNA complex that consist of segments of DNA wrapped around a histone octamer which are then woven into fibres1,2. These chromatin fibres condense the vast amounts of DNA into compact dense structures3,4. Histones proteins are modified via acetylation or deacetylation by histone acetyltransferase HAT and histone deacetylase HDAC enzymes, respectively5,6 to regulate DNA transcription by affecting how tightly DNA strands are bound to histone proteins7. HDACs inhibit transcription by removing N-acetyl modifications on histone lysine residues allowing the histone to carry a positive charge and thereby strengthening its electrostatic interactions with DNA8,9.
Ophthalmologic and facial abnormalities of Nicolaides-Baraitser syndrome
Published in Ophthalmic Genetics, 2022
Russell Simmers, Allison Goodwin, Hind Al Saif, Natario Couser
Nicolaides-Baraitser syndrome (NCBRS) (OMIM # 601358) is a rare autosomal dominant genetic disorder that results from pathogenic variants in the SMARCA2 gene located on chromosome 9p24.3 (1). Several disorders causing intellectual disability, including NCBRS and Coffin-Siris syndrome, are caused by variants in the SWI/SNF chromatin remodeling complex, which loosens chromatin and enhances local transcription using ATP hydrolysis (2). The SMARCA2 gene codes for an ATPase subunit of the SWI/SNF chromatin remodeling complex (3). Missense mutations are the most common cause of NCBRS, though several pathogenic deletions have been reported (4,5). Likewise, pathogenic variations are nearly ubiquitously due to de novo events, but one case of paternal mosaicism inheritance has been reported (6). Features that are now associated with NCBRS were first reported by Nicolaides and Baraitser in 1993 in a 16-year-old patient with severe intellectual disability, sparse hair, and facial and digital dysmorphologies (7). In 1996, Krajewska-Walasek et al. reported the case of a 19-year-old patient with similar symptoms and later in 2003, Morin et al. reported an additional two patients and supported the classification of NCBRS as a new distinct disease (8,9). Over 100 cases of the disorder have now been reported in literature. NCBRS is recognized by a collection of distinct features including sparse scalp hair, microcephaly, course facies, prominent interphalangeal joints, thick distal phalanges, seizures, intellectual disability, and developmental delay (10).