Lecture9DSXinact

X chromosome inactivation in mouse light blue xist

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X chromosome inactivation in mouse Light blue - XIST RNA, red - an X-linked gene (Pgk), dark blue - nuclei B) Pgk gene is expressed from both alleles Later, XIST is strongly expressed from one of X chromosomes Pgk transcription shuts down from that chromosome
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Silencing of one X chromosome by XIST Xi = inactivated X Xic – region from which XIST is transcribed PCR1, PCR2 – Polycomb repressor complexes (should be PRC1, PRC2) Also methylation of promoters of genes
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Covalent modifications are found on histone N-terminus (tail)
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Histone modifications on lysines (K)
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Epigenetic regulation Changes in gene expression that do not result from changes in DNA sequence. Epigenetic changes are preserved when cells divide. Examples of epigenetics: -cell differentiation, from totipotent into specialized cell types --X inactivation Examples of epigenetic modifications: - Histone modifications - DNA methylation
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Activating modifications: H3K4me H3K14ac H3K14ac+ H3S10P Repressive modifications: H3K9me H2AK119ub H3S10P+ H3S28P – chromosomal condensation heterochromatin, silenced genes
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The histone code hypothesis: particular combinations of histone modifications define the conformation of chromatin => transcriptional activity of the DNA. Although there is undoubtedly a strong general correlation, no single histone modification is completely predictive of chromatin state or DNA activity.
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Clicker question Which of the following are expected to be found on the histones of a transcriptionally active gene? A. Acetylation of histone H4 B. Tri-methylation of histone H3 C. Ubiquitination of histone H2A D. Recruitment of PRC complex II
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About 15% of X chromosome genes escape X inactivation. These genes are also present on the Y chromosome, so no dosage compensation for these is normally needed If one X is inactivated anyway, why XXY individuals are not completely healthy? These regions are identical on X and Y, undergo recombination. These regions are called Pseudoautosomal regions (PAR’s)
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X chromosome inactivation in mouse Light blue XIST RNA red...

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