Chromosomal crossover

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome. Crossing over was described, in theory, by Thomas Hunt Morgan. He relied on the discovery of Frans Alfons Janssens who described the phenomenon in 1909 and had called it "chiasmatypie". The term chiasma is linked, if not identical, to chromosomal crossover. Morgan immediately saw the great importance of Janssens' cytological interpretation of chiasmata to the experimental results of his research on t

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Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Giovanni Ciriello, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Elisa Oricchio, Stephanie Jocelyne Sungalee

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. In the present study, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B cells, we show that enhancer-promoter-interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacological depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intrachromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulates interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression. Enhancer-promoter three-dimensional interactions at oncogenic loci are modulated by H3K27ac dynamics. Enhancer hijacking mediated by chromosomal translocations leads to distinct chromatin states, intrachromosomal interactions and allele-specific gene expression.

2021

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Bart Deplancke, Nele Gheldof, Loyse Hippolyte, Marion Leleu

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts’ maps could uncover functionally and clinically related genes.

Springer Nature2017

Telomeric localization of TRF2, a novel human telobox protein

Thierry Laroche

Natural chromosomal ends are stabilized by proteins that bind duplex telomeric DNA repeats. In human cells, the TTAGGG Repeat Factor 1 (TRF1) was identified by two independent studies, one screening for factors that bind duplex telomeric DNA and the other screening for proteins containing a particular Myb motif called the telobox, which is required for telomeric repeat recognition (Fig. 1a; refs 3-5). A second human open reading frame, orf2, contains a telobox sequence and encodes a polypeptide that specifically recognizes mammalian telomeric repeat DNA in vitro. We show that two proteins of 65 and 69 kD, expressed in HeLa cells, contain the orf2 telobox sequence. These proteins are collectively termed TRF2. Affinity-purified antibodies specific for anti-TRF2 label the telomeres of intact human chromosomes, strengthening the correlation between occurrence of telobox and telomere-repeat recognition in vivo.

1997

Meiosis

Meiosis (maɪˈoʊsɪs; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. I

Homologous recombination

Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (u

Homologous chromosome

A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes i