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Epigenetics from Oocytes to Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Dagnė Daškevičiūtė, Marta Sanchez-Delgado, David Monk
The nucleus of an interphase cell contains chromatin organized into a hierarchical structure that is key for most biological events, including transcription. DNA can form loops bringing distal regulatory elements into close proximity with promoters. These looping events are constrained within self-interacting genomic regions known as topologically associated domains (TADs). The recent development of low-input Hi-C based on the 3C (chromosome conformation capture) method has revealed the dynamic nature of the genome architecture during pre-implantation development58,59 (Figure 9.3a). The meiotic chromatin of MII mouse oocytes generally lacks TAD structures, whereas sperm present with both, TADs and A/B compartments, which largely correspond to gene-rich and repressive chromatin intervals respectively, and likely reflect protamine packaging.58 Following fertilization, the higher-order structures are gradually created, with the establishment of maternal genome being weaker than the paternal, with TAD formation dependent upon DNA replication rather than EGA59,60 (Figure 9.3b). In humans, sperm lack three-dimensional genome architecture and TADs, which is largely due to the absence of CTCF, which only becomes expressed following EGA, coinciding with TADs and A/B compartmentation.61 Unlike in a mouse, TAD establishment in pre-implantation embryos appears to be EGA-dependent, suggesting that the mechanisms of establishing chromatin structures differ between mammalian species.59–61
DNA Methods in Veterinary Medicine
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Lastly, another approach to genome assembly is the use of Hi-C, so named because it uses high-throughput sequencing on chromatin. Hi-C is a form of chromatin confirmation techniques. It uses the way that DNA is wound around chromatin to gain information about that DNA. In this method, chromatin is isolated with the bound DNA. Formaldehyde is added, which causes the different pieces of DNA that are close to each other to link together. More links will occur with nearby sequences than distant ones. After the formaldehyde step, the DNA is digested with one or more restriction enzymes, which leaves the linked DNA pieces stuck together. Those linked fragments are then ligated together to form chimeric molecules whose ends originate at different positions along the chromosome (Dudchenko et al., 2018). After standard paired-end Illumina sequencing the number of near to distant joins can be determined by comparing the reads to scaffolds generated by other methods described above. Hi-C has been used to assemble genomes for dozens of animals (e.g., Humble et al., 2019; see also, DNAzoo.org).
Cytogenetic and molecular genetic methods for chromosomal translocations detection with reference to the KMT2A/MLL gene
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Nikolai Lomov, Elena Zerkalenkova, Svetlana Lebedeva, Vladimir Viushkov, Mikhail A. Rubtsov
Although both Hi-C and WGS rely on NGS, Hi-C has two advantages over WGS for the detection of chromosomal translocations. First, the spatial contacts between two regions that flank a breakpoint are spread across several megabases [134]; therefore, the necessary sequencing depth for detecting translocation by HiC is lower than that for WGS [131], which significantly reduces the cost of analysis. To reduce the cost even further, enrichment may be applied to a Hi-C library to analyze contacts only between certain regions, such as exons or promoters [134]. Although the resolution of Hi-C is hundreds of kilobases or even megabases, the sequence of a breakpoint may be extracted by analyzing reads with prior knowledge of the approximate breakpoint position, based on Hi-C data [135]. Second, Hi-C allows translocations to be detected in repetitive regions of the genome. Chromatin contacts may span beyond repetitive regions, making translocations detectable even if the breakpoints are missed [135].
Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions
Published in Nanotoxicology, 2018
Yuxiang Sun, Hui Dai, Shaopeng Chen, Ming Xu, Xuanyu Wang, Yajun Zhang, Shengmin Xu, An Xu, Jian Weng, Sijin Liu, Lijun Wu
Surface properties (e.g. functional groups, charge, carbon/oxygen ratio, and hydrophobicity) are crucial determinants of the biocompatibility of GO (Yang et al. 2013). For example, PEGylation has been preferentially used to modify nanomaterials to reduce nonspecific protein adsorption, preventing flocculation, opsonization, and subsequent complement activation (Aggarwal et al. 2009). Compared to pristine GO, PVP-coated GO exhibits lower immunotoxicity and significantly delays the apoptotic process of T lymphocytes (Zhi et al. 2013). Besides PEGylation and PVP, other chemical functionalization and polymer modifications of GO have been explored to improve safety (Kontos and Hubbell 2012). Nonetheless, little is known about the role of GO materials in dynamic higher-order chromatin structure. To investigate the role of GO modifications, we compared the effects of three different GO materials on the chromatin structures. GO-PAA had a lower ability to alter the chromatin architecture than those of other GO derivatives, suggesting that chemical modification is potentially important in the regulation of GO-induced biological effects. Although our research fully demonstrated that GO-mediated dynamic chromatin looping was required for gene expression, analyzes of other classical ENMs are needed. Importantly, more advanced techniques, such as Hi-C, might be useful to determine changes in genome-wide chromatin spatial structure caused by ENM exposure. It would be of great practical significance to reveal the toxicity of ENMs from the perspective of epigenetic regulation.
The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Filip Machaj, Jakub Rosik, Bartosz Szostak, Andrzej Pawlik
Disease-associated genetic variants may also be searched using chromatin conformation capture technology (Capture Hi-C). Mifsud et al. used Capture Hi-C, which is an adapted genome conformation assay, to examine the long-range interactions of promoters in human blood cells. These authors demonstrated that interacting loci are enriched in disease-associated SNPs, and distal mutations might disrupt the regulation of relevant genes [97].