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Summer 2007 Workshop in Biology and Multimedia for High School Teachers

Summer 2007 Workshop in Biology and Multimedia for High School Teachers. Barr Body: X Chromosome Inactivation. By: E.A. Struzziero. http://faculty.uca.edu/~johnc/Barr%20Body%20Cat.jpg. Murray L. Barr and E. G. Bertram  1949  Dark, drumstick-shaped masses in nuclei of nerve cells

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Summer 2007 Workshop in Biology and Multimedia for High School Teachers

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  1. Summer 2007 Workshop • in Biology and Multimedia • for High School Teachers

  2. Barr Body:X Chromosome Inactivation By: E.A. Struzziero

  3. http://faculty.uca.edu/~johnc/Barr%20Body%20Cat.jpg.

  4. Murray L. Barr and E. G. Bertram 1949 Dark, drumstick-shaped masses in nuclei of nerve cells Pattern only seen in cats History

  5. History • Mary Lyon 1961 The Lyon Hypothesis (Lyonization) definition: condensation of X chromosome mechanism for inactivating the genes on the chromosome Named inactive X chromosome a Barr body www.biologyreference.com/Re-Se/Sex-Chromosome.html

  6. http://biology.clc.uc.edu/graphics/bio105/barr.jpg

  7. Process • Random selection of X chromosome Inactive throughout cell’s lifetime Xa = active X chromosome Xi = inactive X chromosome

  8. cen Process • X inactivation center (XIC) Near centromere Contains 12 genes • 7 genes code for proteins • 5 genes code for untranslated RNA (Rougeulle et al., 2003) XIC

  9. Process • Xist and Tsix Two genes actively involved in inactivating an X chromosome Antagonistic roles • Xi  Xist expression  Tsix expression • Xa  Xist expression  Tsix expression (Lee et al., 1999)

  10. cen Xist/Tsix in XIC Process • Xist and Tsix Only genes expressed on Xi X chromosome lacking Xist gene cannot be inactivated

  11. Xa Xi cen cen Xist RNA Process • Xist gene (pronounced “exist”) Encodes a large RNA molecule • Coats Xi from the XIC near the centromere outward along the X chromosome (Lyon, 2003)

  12. Process • Mechanism for compacting Xi (Barr body) Enzymes cause the following to occur: • High levels of DNA methylation (CH3) (Chadwick et al., 2003) • Low levels of histone substitution of the acetyl group (CH3CO) for a H atom in a -OH group (www.en.wikipedia.org/wiki/Acetylation)

  13. Xa Xi cen cen CH3 CH3 CH3 CH3 CH3 Xist RNA CH3 CH3 CH3 CH3 CH3

  14. Xa cen cen Xi Process High levels of histone H2A everywhere (deNapoles et al., 2004) High levels of histone H3 methylation (Heard et al., 2001) H2A H3

  15. Barrbody: Source, BIODIDAC, University of Ottawa. http://biodidac.bio.uottawa.ca

  16. REFERENCES • Barrbody: Source, BIODIDAC, University of Ottawa. • http://biodidac.bio.uottawa.ca • Accessed on 7/12/07 • Brown,C.J., Robinson,W.P., (1997), XIST Expression and X-Chromosome Inactivation in Human Preimplantation Embryos. Am. J. Hum. Genet. 61, 5-8 (Full Text PDF • Carrel L, Willard H (2005). "X-inactivation profile reveals extensive variability in X-linked gene expression in females". Nature434 (7031): 400-4. PMID 15772666.  • Chadwick,B.P., Willard,H.F., (2003), Barring gene expression after XIST: maintaining faculative heterochromatin on the inactive X. j.semcdb 14, 359-367 (Abstract)

  17. REFERENCES • de Napoles,M., Mermoud,J.E., Wakao,R., Tang,Y.A., Endoh,M., Appanah,R., Nesterova,T.B., Silva,J., Otte,A.P., Vidal,M., Koseki,H., Brockdorff,N., (2004), Polycomb Group Proteins Ring1A/B Link Ubiquitylation of Histone H2A to Heritable Gene Silencing and X Inactivation. Dev. Cell 7, 663-676 (Abstract) • Hall,L.L., Lawrence,J.B., (2003), The Cell Biology of a Novel Chromosomal RNA: Chromosome Painting By XIST/Xist RNA Initiates a remodeling cascade. j.semcdb 14, 369-378 (Abstract) • Heard, E., Rougeulle, C., Arnaud, D., Avner, P., Allis, C. D. (2001), Methylation of Histone H3 at Lys-9 Is an Early Mark on the X Chromosome during X Inactivation. Cell 107, 727-738. (Full Text)

  18. REFERENCES • Lee, J. T., Davidow, L. S., Warshawsky, D., (1999), Tisx, a gene antisense to Xist at the X-inactivation centre. Nat. Genet. 21, 400-404. (Full Text) • Lee, J. T., (2003), X-chromosome inactivation: a multi-disciplinary approach. j.semcdb 14, 311-312. (doi:10.1016/j.semcdb.2003.09.025 (Abstract) • Lyon, M. (1961). "Gene action in the X-chromosome of the mouse (Mus musculus L.)". Nature 190: 372-3. PMID 13764598 • Lyon, M. F., (2003), The Lyon and the LINE hypothesis. j.semcdb 14, 313-318. (Abstract)

  19. REFERENCES • Rougeulle, C., Avner, P. (2003), Controlling X-inactivationin mammals: what does the centre hold?. j.semcdb 14, 331-340. (Abstract) • Whitelaw, Emma, “Unravelling the X in Sex”. Developmental Cell 11, 759-762, December 2006. (Full Text) Special thanks to Christine Rodriguez of HHMI-Outreach Program At Harvard University’s Department of Molecular & Cellular Biology with the graphics.

  20. REFERENCES • http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Genetics-%20Chromosomes/non-mend.htm Accessed on 7/13/07 • http://biology.clc.uc.edu/graphics/bio105/barr.jpg Accessed on 7/12/07(free image) • http://faculty.uca.edu/~johnc/Barr%20Body%20Cat.jpg. Accessed on 7/12/07 • www.whonamedit.com/doctor.cfm/2473.html. Accessed 7/13/07 • www.biologyreference.com/Re-Se/Sex-Chromosome.html) Accessed 7/13/07 • www.en.wikipedia.org/wiki/Acetylation Accessed 7/12/07

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