Name: genomic imprinting in human disease
Uploaded: 2020-11-23T11:47:38.000Z
Duration: 2 min 30 s
Channel: JoVE

L'empreinte génomique parentale est un phénomène où la régulation de l'expression génique 00:00:05.180 00:00:00:00:10.040 connus sous le nom de master regulator Ces master regulators favorisent ou inhibent la transcription de groupes de gènes, tels que ceux requis pour la différenciation cellulaire. Ces protéines importantes peuvent fonctionner soit directement ou indirectement pour réguler l'expression du gène. Les master regulators peuvent se lier directement aux séquences cis-réglatrices pour contrôler la transcription de plusieurs gènes impliqués dans les réponses cellulaires connexes.MyoD est un master regulator de transcription requis pour la différenciation des cellules musculaires. Il se lie aux séquences cis-régulatrices d'une centaines de gènes impliqués dans le développement musculaire, y compris la chaîne lourde de la myosine, une protéine motrice trouvée dans le muscle, et la desmine, un filament intermédiaire spécifique du muscle. Les master regulators peuvent également agir indirectement par liaison à des séquences cis-régulatrices qui qui contrôlent la production d'autres facteurs de transcription.MyoD se lie à des séquences régulatrices qui induisent l'expression d'autres facteurs de transcription, tels que le facteur activateur spécifique des myocytes, qui régule les gènes supplémentaires nécessaires au développement et à la réparation des tissus musculaires. Les master regulators travaillent souvent ensemble pour promouvoir la différenciation cellulaire. Les master regulators Oct4 et Sox2 travaillent ensemble pour réguler l'expression de ZFP-206.Ce facteur de transcription doit être fortement exprimé dans les cellules souches embryonnaires de souris et d'humains pour déclencher la différenciation cellulaire. De même, ensemble, PPAR-gamma et C/EBP-alpha déclenchent le développement des adipocytes ou des cellules graisseuses par liaison vers les sites de régulation cis pour les protéines spécifiques aux adipocytes. En outre, PPAR-gamma et C/EBP-alpha se lient chacun à un site de régulation de la transcription pour l'autre, créant une boucle de rétroaction positive pour augmenter la transcription pendant la différenciation.

<ol>
	<li>Butler, M. G. (2009). Troubles de l’empreinte génomique chez l’homme : une mini-revue. Journal de la reproduction assistée et de la génétique, 26(9-10), 477-486.</li>
	<li>Lobo, I. (2008) Empreinte génomique et modèles d’hérédité de la maladie. Éducation à la nature 1(1) :66</li>
</ol>

empreinte génomique et héritage

Genomic Imprinting and Inheritance

Les organismes diploïdes héritent du matériel génétique via les chromosomes des deux parents. Les copies du même gène sont appelées allèles. Dans la plupart des cas, les deux allèles sont exprimés simultanément et permettent à divers processus cellulaires de fonctionner de manière optimale. Si l’un des allèles est manquant ou muté, l’expression de l’autre allèle peut compenser ; cependant, cela n’est pas vrai pour tous les gènes.

L'expression de certains gènes dépend du parent qui a transmis le gène à sa progéniture, par le biais d'un phénomène appelé empreinte génomique. Dans l'empreinte génomique, l'ADN codant pour le gène ou sa séquence régulatrice est imprimé avec des étiquettes chimiques telles que des groupes méthyle, uniquement dans la copie héritée d'un parent particulier. Cette étiquette résiste à la déméthylation lors de la fécondation et est transmise à la progéniture pour une expression génique sélective.

Parfois, deux copies du gène sont héritées du même parent et le gène de l’autre parent est absent. La disomie maternelle uniparentale se produit lorsque deux copies du gène de la mère sont présentes ; en revanche, la disomie uniparentale paternelle se produit lorsque deux copies sont héritées du père. S’il existe deux copies de l’allèle silencieux et si l’allèle typiquement exprimé est absent, cela conduit souvent à une maladie génétique.

Maladies humaines liées à l'empreinte génomique

Les maladies chez l'homme liées à l'empreinte génomique comprennent le syndrome de Beckwith-Wiedemann, le syndrome d'Angelman, le syndrome de Prader-Willi et certains cancers.

Les syndromes de Prader-Willi et d'Angelman sont tous deux associés au chromosome 15. Le syndrome de Prader-Willi survient en cas de disomie maternelle uniparentale. Les personnes atteintes de ce syndrome peuvent présenter une obésité, un sous-développement sexuel et un handicap mental. Le syndrome d'Angelman est associé à une disomie paternelle uniparentale. Les personnes atteintes de ce syndrome peuvent présenter des handicaps mentaux, des déficits de développement, des troubles du sommeil et une hyperactivité.

Empreinte génomique et héritage

Les organismes diploïdes héritent du matériel génétique par le biais des chromosomes des deux parents. Les copies d’un même gène sont appelées allèles. Dans la plupart des cas, les deux ...

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genomic imprinting in human disease

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way.

In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are resistant to demethylation during fertilization. That means the imprint can survive into the offspring and help control which allele is expressed.

Problems can occur when both copies of a gene come from the same parent. Maternal uniparental disomy means two maternal copies are present, while paternal uniparental disomy means two paternal copies are present. If the active allele is missing and the silenced allele is inherited twice, a genetic disorder may result.

Human diseases linked to genomic imprinting include Beckwith-Wiedemann syndrome, Angelman syndrome, Prader-Willi syndrome, and some cancers. Prader-Willi syndrome is associated with maternal uniparental disomy of chromosome 15. It can cause obesity, sexual under-development, and mental disabilities. Angelman syndrome is linked to paternal uniparental disomy of chromosome 15. It may cause mental disabilities, developmental deficiencies, sleep disorders, and hyperactivity.

Genomic Imprinting in Human Disease

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

regulation of expression occurs at multiple steps

regulation-of-expression-occurs-at-multiple-steps

How Cells Control Gene Expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

How Transcription Activators Turn Genes On

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

eukaryotic transcription inhibitors

How Eukaryotic Gene Repressors Work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Reprogramming Cells into Stem Cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Learn how genomic imprinting controls gene expression and why maternal or paternal uniparental disomy can lead to disorders such as Prader-Willi and Angelman syndromes.

Genomic Imprinting in Human Disease | JoVE K12

molecular biology

JoVE Core Biologie Moléculaire illustre les processus moléculaires au sein de la cellule grâce à des leçons vidéos claires et concises. Les applications de ces concepts sont ensuite démontrées grâce à des expériences concrètes en laboratoire.

Genomic Imprinting in Human Disease

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