Epigenetic silencing of X-chromosome

Kužet, Sanya Eduarda (2012) Epigenetic silencing of X-chromosome. Bachelor's thesis, Faculty of Science > Department of Biology.

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Abstract

X chromosomes are sex chromosomes that carry a large number of genes which control different metabolic pathways. In female mammals, there is a mechanism of dosage compensation due to the existence of two X chromosomes. Double amount of genes would represent a problem for an individual. The dosage compensation involves an inactivation process of one of the two X chromosome. The inactivation occurs around 16th day of embryonic development when inactive X chromosome is silenced by packaging into transcriptionally inactive heterochromatin. X inactivation center (XIC) is a short segment of X chromosome that is involved in inactivation. It represents the initiation site from which inactivation spreads to the rest of the chromosome. XIC contains four genes, Xist, Tsix, and Jpx FTX, from which the most important is Xist. Xist gene is expressed from inactive X chromosome and produces a large non-coding RNA that is responsible for silencing of X chromosome. Xist RNA coats the chromosome and thus prevents the expression of its genes. Hypoacetylation of histones is also connected with silencing of X chromosome. Inactive chromosome has a low level of acetylated histones H2A, H3 and H4. Increase in Xist gene expression and beginning of X chromosome inactivation happens two days before histone deacetylation. DNA methylation is also involved in epigenetic silencing of X chromosme, it occurs during DNA synthesis and it's limited to the CpG dinucleotides. Analysis of CpG island of Xist gene promoter shows that the silenced allele on active chromosome is hypermethylated, while the expressed allele on active chromosome is hypomethylated. About 15% of the total number of genes on X chromosome remains transcriptionally active and contains epigenetic marks of active chromatin. Inactive, heterochromatinized X chromosome occur as heteropicnotic body called Barr's body near nuclear envelope of interphase nuclei. Fenotypic evidence for X-chromosome inactivation is coat colours of various mammals, including calico cat – only a female cat has coat that consist of mosaic patches of both oragne and black colour. This phenomenon is called the mosaic expression and depends on the differential expression of alleles on X chromosome.

Item Type: Thesis (Bachelor's thesis)
Supervisor: Zoldoš, Vlatka
Date: 2012
Number of Pages: 15
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 23 Oct 2014 11:32
Last Modified: 23 Oct 2014 11:32
URI: http://digre.pmf.unizg.hr/id/eprint/3144

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