China
Africa
Explore chapters and articles related to this topic
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].
Muscle Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Kourosh Rezania, Peter Pytel, Betty Soliven
The skeletal muscle may show nonspecific myopathic changes including an increase in myofiber size, an increased number of myofibers with internalized nuclei, and mild features of myofiber degeneration/regeneration. EMD1 cases usually indicate a loss of emerin expression on immunocytochemical analysis. LMNA gene mutations, however, typically show preserved expression of lamin A/C. Some studies have described irregularities of the nuclear membrane and the peripheral arrangement of heterochromatin by electron microscopy.
Sex Chromosome Pairing and Fertility in the Heterogametic Sex of Mammals and Birds
Published in Christopher B. Gillies, Fertility and Chromosome Pairing: Recent Studies in Plants and Animals, 2020
In three Gerbillus species, the X and Y chromosomes are both translocated with an autosomes, which constitute their short arms in two of the species (the third species bears a pericentric inversion).108 The regions corresponding to the translocated autosomes form regular SCs, while those corresponding to the original X and Y axes remain single.108 These different regions are joined by a lightly stained, small stretch of single axis, which is assumed to correspond to an intercalated C+ band. The autosomal and gonosomal segments behave independently, the latter showing typical heteropycnosis and axial differentiations. In a fourth species (Taterillus pygargus), both sex chromosomes are involved in an additional translocation at the free ends, but again, the gonosomal segments behave independently of the autosomal ones. It has been assumed108 that the intercalated heterochromatin acts as an isolator, and thus relieves the male meiotic cells from the harmful effects of the spreading of inactivation from the sex chromosomes or their reactivation by autosomes.
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.
Heterochromatin extension: a possible cytogenetic fate of primary amenorrhea along with normal karyotype
Published in Journal of Obstetrics and Gynaecology, 2022
Bishal Kumar Dey, Shanoli Ghosh, Ajanta Halder, Somajita Chakraborty, Sanchita Roy
The region of heterochromatin also acts as a key part in chromosome structure, histone modification and gene regulation. There is evidence from where we come to know that there may be displacement of heterochromatin from one chromosome to another. Perhaps, this displacement is helping in the extension of a particular chromosome at the heterochromatin portion of the long arm (Bannister and Kouzarides 2011). The mechanisms of spindle fibres, chromosome movement, meiosis crossover and change of sister chromatids are considered to be the integral region as heterochromatin for a chromosome. At the time of meiosis, there may be a change in area of synapses of homologous chromosomes in the polymorphic heterochromatin region. The heterochromatin in chromosomal polymorphism can also regulate gene expression by reversible transformation between heterochromatin (non-coding DNA sequences) and euchromatin (expressed DNA sequences) thus justifying certain clinical expression like short stature or PA. It was also postulated that defective histone protein methylation due to presence of heteromorphic variants may play a more crucial role in ovarian failure. Association of heterochromatin polymorphism with ovarian dysgenesis may be a reason for the occurrence of PA. For that, we need to study on a greater number of patients on the basis of their nucleosome’s functionality and heteromorphic polymorphism by sequencing.
An expert overview of emerging therapies for acute myeloid leukemia: novel small molecules targeting apoptosis, p53, transcriptional regulation and metabolism
Published in Expert Opinion on Investigational Drugs, 2020
Kapil Saxena, Marina Konopleva
Histones (H2A, H2B, H3, and H4) are proteins that assemble as an octamer (two of each) around which DNA wraps to form a nucleosome, the functional subunit of chromatin [82]. Chromatin typically exists in one of two major states – euchromatin and heterochromatin. While heterochromatin is tightly packaged and thereby more sterically restricted from transcriptional machinery, euchromatin has a more open conformation that is less condensed and more accessible to transcriptional complexes [82,83]. The transition between different chromatin states is partially mediated by histone modification. A major type of histone modification is acetylation/deacetylation. Histone acetylation can attract scaffolding proteins and enzymes involved in transcription. Enzymes that acetylate histones are termed histone acetyltransferases (HATs), and those that remove acetyl groups from histones are known as histone deacetylases (HDACs) [4,82–84]. Once histones are modified by acetylation, these changes need to be interpreted by other proteins for transcriptional regulation. Proteins that contain bromodomain (BRD) structures represent a class of proteins that can ‘read’ histone acetylation sites and indirectly regulate RNA polymerase II-mediated transcription [82,85].