Bivalent (genetics)

Last updated September 23, 2024

In cellular biology, a bivalent is one pair of chromosomes (homologous chromosomes) in a tetrad. A tetrad is the association of a pair of homologous chromosomes (4 sister chromatids) physically held together by at least one DNA crossover. This physical attachment allows for alignment and segregation of the homologous chromosomes in the first meiotic division. In most organisms, each replicated chromosome (composed of two identical sisters chromatid) elicits formation of DNA double-strand breaks during the leptotene phase. These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.

Formation

The formation of a bivalent occurs during the first division of meiosis (in the zygotene stage of meiotic prophase 1). In most organisms, each replicated chromosome (composed of two identical sister chromatids ^[1]^[2]) elicits formation of DNA double-strand breaks during the leptotene phase.^[3] These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.^[4] Resolution of the DNA recombination intermediate into a crossover exchanges DNA segments between the two homologous chromosomes at a site called a chiasma (plural: chiasmata). This physical strand exchange and the cohesion between the sister chromatids along each chromosome ensure robust pairing of the homologs in diplotene phase. The structure, visible by microscopy, is called a bivalent.^[5] Resolution of the DNA recombination intermediate into a crossover exchanges DNA segments between the two homologous chromosomes at a site called a chiasma (plural: chiasmata). This physical strand exchange and the cohesion between the sister chromatids along each chromosome ensure robust pairing of the homologs in diplotene phase. The structure, visible by microscopy, is called a bivalent. An intricate molecular machinery is at the core of gene expression regulation in every cell. During the initial stages of organismal development, the coordinated activation of diverse transcriptional programs is crucial and must be carefully executed to shape every organ and tissue. Bivalent which promoters and poised enhancers are regulatory regions decorated with histone marks that are associated with both positive and negative transcriptional outcomes. Finally, we highlight the potential link between bivalency and cancer which could drive biomedical research in disease etiology and treatment.

The information of a one gene should be the different in executive way in the cell types to achieve main program in this diversity. Chromatin is carrier of the instructions and also the DNA surrounded by the histones shows impact of the nucleosome which we can see this is the basic unit. The packed gives information for regulation nucleosome of physical barrier they show impact on the chromatin remodelers parts N- terminal parts of histone particle, histone tails, covalent post-translational modifies and also creates an epigenetics of [PCG] and [TRXG] plays an initial role these mutations caused in groups from transformation in Drosophila shows a clearcut information

Structure

A bivalent is the association of two replicated homologous chromosomes having exchanged DNA strand in at least one site called chiasmata. Each bivalent contains a minimum of one chiasma and rarely more than three. This limited number (much lower than the number of initiated DNA breaks) is due to crossover interference, a poorly understood phenomenon that limits the number of resolution of repair events into crossover in the vicinity of another pre-existing crossover outcome, thereby limiting the total number of crossovers per homologs pair.^[4] Bivalent gene is a gene marked with both H3K4me3 and H3K27me3 epigenetic modification in the same area of this kind and is proposed to play a pivotal role related to pluripotency in embryonic stem (ES) cells. Bivalent promoters marked with both H3K27me3 and H3K4me3 histone modifications are characteristic of poised promoters in embryonic stem (ES) cells. The model of poised promoters postulates that bivalent chromatin in ES cells is resolved to Mono valency upon differentiation. With the availability of single-cell RNA sequencing (scRNA-seq) data, subsequent switches in transcriptional state at bivalent promoters can be studied more closely.

Function

At the meiotic metaphase I, the cytoskeleton puts the bivalents under tension by pulling each homolog in opposite direction (contrary to mitotic division where the forces are exerted on each chromatid). The anchorage of the cytoskeleton to the chromosomes takes place at the centromere thanks to a protein complex called kinetochore. This tension results in the alignment of the bivalent at the center of the cell, the chiasmata and the distal cohesion of the sister chromatids being the anchor point sustaining the force exerted on the whole structure. Impressively, human female primary oocytes remains in this tension state for decades (from the establishment of the oocyte in metaphase I during embryonic development, to the ovulation event in adulthood that resume the meiotic division), highlighting the robustness of the chiasma and the cohesion that hold the bivalents together. The cell transcription regulates of developmental genes We develop an approach for capturing genes undergoing transcriptional switching by detecting 'bimodal' gene expression patterns from scRNA-seq data. We integrate the identification of bimodal genes in ES cell differentiation with analysis of chromatin state and for kind of then identify clear cell-state dependent patterns of bimodal, bivalent genes. We show that binarization of bimodal genes can be used to identify differentially expressed genes from fractional ON/OFF proportions. In time series data from differentiating cells, we build a pseudo time approximation and use a hidden Markov model to infer gene activity switching pseudo times, which we use to infer a regulatory network. We identify pathways of switching during differentiation, novel details of those pathway, and transcription factor coordination with downstream targets.

Conclusions: Genes with expression levels too low to be informative in conventional scRNA analysis can be used to infer transcriptional switching networks that connect transcriptional activity to chromatin state. in with analysis of chromatin state and for kind of then identify clear cell-state dependent patterns of bimodal, bivalent genes. We show that binarization of bimodal genes can be used to identify differentially expressed genes from fractional ON/OFF proportions. In time series data from differentiating cells, we build a pseudo time approximation and use a hidden Markov model to infer gene activity switching pseudo times, which we use to infer a regulatory network. We identify pathways of switching during differentiation, novel details of those pathway, and transcription factor coordination with downstream targets. This offers a novel and productive means of inferring regulatory networks from scRNA-seq data.

Keywords: Bimodality; Bivalency; Chromatin state; Embryonic stem cells; Genome regulatory network; Hidden Markov model; Pseudo time; scRNA-seq.

Related Research Articles

Meiosis (; from Ancient Greek μείωσις 'lessening', is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy of each chromosome. Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a zygote, a cell with two copies of each chromosome again.

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.

Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

A pair of homologous chromosomes, or homologs, is 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 in the same loci, where they provide points along each chromosome that enable a pair of chromosomes to align correctly with each other before separating during meiosis. This is the basis for Mendelian inheritance, which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.

Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another.

A heteroduplex is a double-stranded (duplex) molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from different sources, such as from different homologous chromosomes or even from different organisms.

The synaptonemal complex (SC) is a protein structure that forms between homologous chromosomes during meiosis and is thought to mediate synapsis and recombination during prophase I during meiosis in eukaryotes. It is currently thought that the SC functions primarily as a scaffold to allow interacting chromatids to complete their crossover activities.

Synapsis or Syzygy is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. When homologous chromosomes synapse, their ends are first attached to the nuclear envelope. These end-membrane complexes then migrate, assisted by the extranuclear cytoskeleton, until matching ends have been paired. Then the intervening regions of the chromosome are brought together, and may be connected by a protein-DNA complex called the synaptonemal complex. During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome.

A chromomere, also known as an idiomere, is one of the serially aligned beads or granules of a eukaryotic chromosome, resulting from local coiling of a continuous DNA thread. Chromomeres are regions of chromatin that have been compacted through localized contraction. In areas of chromatin with the absence of transcription, condensing of DNA and protein complexes will result in the formation of chromomeres. It is visible on a chromosome during the prophase of meiosis and mitosis. Giant banded (Polytene) chromosomes resulting from the replication of the chromosomes and the synapsis of homologs without cell division is a process called endomitosis. These chromosomes consist of more than 1000 copies of the same chromatid that are aligned and produce alternating dark and light bands when stained. The dark bands are the chromomere.

Zygotene is the second stage of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes. It follows the Leptotene stage and is followed by Pachytene stage.

The pachytene stage, also known as pachynema, is the third stage of prophase I during meiosis, the specialized cell division that reduces chromosome number by half to produce haploid gametes. It follows the zygotene stage and is followed by the stage Diplotene

Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

MutS protein homolog 4 is a protein that in humans is encoded by the MSH4 gene.

In genetics, a chiasma is the point of contact, the physical link, between two (non-sister) chromatids belonging to homologous chromosomes. At a given chiasma, an exchange of genetic material can occur between both chromatids, what is called a chromosomal crossover, but this is much more frequent during meiosis than mitosis. In meiosis, absence of a chiasma generally results in improper chromosomal segregation and aneuploidy.

The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed.

In cell biology, meiomitosis is an aberrant cellular division pathway that combines normal mitosis pathways with ectopically expressed meiotic machinery resulting in genomic instability.

The leptotene stage, also known as leptonema, is the first of five substages of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes in sexually reproducing organisms.

Achiasmate meiosis refers to meiosis without chiasmata, which are structures that are necessary for recombination to occur and that usually aid in the segregation of non-sister homologs. The pachytene stage of prophase I typically results in the formation of chiasmata between homologous non-sister chromatids in the tetrad chromosomes that form. The formation of a chiasma is also referred to as crossing over. When two homologous chromatids cross over, they form a chiasma at the point of their intersection. However, it has been found that there are cases where one or more pairs of homologous chromosomes do not form chiasmata during pachynema. Without a chiasma, no recombination between homologs can occur.

References

↑ Lefers, Mark. "Northwestern University Department of Molecular Biosciences" . Retrieved 26 September 2015.
↑ "University of Arizona Department of Biochemistry and Molecular Biophysics". The Biology Project. Retrieved 26 September 2015.
↑ Padmore, R.; Cao, L.; Kleckner, N. (1991-09-20). "Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae". Cell. 66 (6): 1239–1256. doi:10.1016/0092-8674(91)90046-2. ISSN 0092-8674. PMID 1913808. S2CID 20771360.
1 2 Zickler, Denise; Kleckner, Nancy (2015-06-01). "Recombination, Pairing, and Synapsis of Homologs during Meiosis". Cold Spring Harbor Perspectives in Biology. 7 (6): a016626. doi:10.1101/cshperspect.a016626. ISSN 1943-0264. PMC 4448610 . PMID 25986558.
↑ Jones, Gareth H.; Franklin, F. Chris H. (2006-07-28). "Meiotic crossing-over: obligation and interference". Cell. 126 (2): 246–248. doi: 10.1016/j.cell.2006.07.010 . ISSN 0092-8674. PMID 16873056.

Blanco E., Gonzalez Ramirez M., Alcaine-colet , A., Aranda the bivalent genome ; characterization structure trends in genetics

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[NWedu-1] Lefers, Mark. "Northwestern University Department of Molecular Biosciences" . Retrieved 26 September 2015.

[ARedu-2] "University of Arizona Department of Biochemistry and Molecular Biophysics". The Biology Project. Retrieved 26 September 2015.

[3] Padmore, R.; Cao, L.; Kleckner, N. (1991-09-20). "Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae". Cell. 66 (6): 1239–1256. doi:10.1016/0092-8674(91)90046-2. ISSN 0092-8674. PMID 1913808. S2CID 20771360.

[Zickler-2015-4] 1 2 Zickler, Denise; Kleckner, Nancy (2015-06-01). "Recombination, Pairing, and Synapsis of Homologs during Meiosis". Cold Spring Harbor Perspectives in Biology. 7 (6): a016626. doi:10.1101/cshperspect.a016626. ISSN 1943-0264. PMC 4448610 . PMID 25986558.

[5] Jones, Gareth H.; Franklin, F. Chris H. (2006-07-28). "Meiotic crossing-over: obligation and interference". Cell. 126 (2): 246–248. doi: 10.1016/j.cell.2006.07.010 . ISSN 0092-8674. PMID 16873056.

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