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X-Inactivation

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.

X-inactivation

X-inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.

Inheritance of Chromatin Structures

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...

Dosage Compensation

Dosage Compensation

In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...

Epigenetic Regulation

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.

Epigenetic Regulation

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

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Related Experiment Video

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A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome

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The DXPas34 repeat regulates random and imprinted X inactivation.

Dena E Cohen¹, Lance S Davidow, Jennifer A Erwin

¹Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Developmental Cell

|January 3, 2007

Summary

The DXPas34 repeat regulates Xist RNA

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Published on: June 14, 2014

Area of Science:

Genetics
Epigenetics
Molecular Biology

Background:

X chromosome inactivation (XCI) is crucial for dosage compensation in female mammals.
The noncoding RNA Xist initiates XCI, while its antisense partner, Tsix, regulates this process.
Understanding Tsix regulation is key to deciphering XCI mechanisms.

Purpose of the Study:

To investigate the role of the DXPas34 repeat within the Tsix gene.
To elucidate the regulatory functions of DXPas34 in XCI.
To determine the necessity of DXPas34 for both random and imprinted XCI.

Main Methods:

Generation of three new Tsix alleles in mouse embryonic stem cells.
Analysis of DXPas34 promoter activity and transcript production.
Assessment of Tsix regulation during XCI.
Germline transmission studies of mutated DXPas34 alleles.

Main Results:

DXPas34 exhibits bidirectional promoter activity, producing overlapping transcripts.
The Tsix promoter is dispensable for XCI, but DXPas34 plays critical dual roles.
DXPas34 acts as an enhancer for Tsix during XCI initiation and a repressor for stable silencing.
Mutations in DXPas34 disrupt both random and imprinted XCI in mice.

Conclusions:

DXPas34 is essential for regulating Tsix function during XCI.
DXPas34 possesses a unique dual enhancer-repressor activity crucial for XCI.
The retrotransposon-like nature of DXPas34 suggests an ancient mechanism for gene regulation.