Transcript Document
• 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
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History
Murray L. Barr and E. G. Bertram 1949 Dark, drumstick-shaped masses in nuclei of nerve cells Pattern only seen in cats www.whona medit.com/doctor.cfm/2473.html
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
Quic kTime™ and a TIFF (Unc ompres sed) dec ompres sor are needed to see t his pic ture.
http://biology.clc.uc.edu/graphics/bio105/barr.jpg
Process
• Random selection of X chromosome Inactive throughout cell’s lifetime Xa = active X chromosome Xi = inactive X chromosome
faculty. clintoncc.suny. edu/ .../files/Bio%20101/ Bio%20101%20Lectures/Genetics-%20Chromosomes/non-mend.htm - 21k Accessed on July 12 , 2007. Courtsey o f Michael J. Gregory, Ph.D.
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) cen XIC
Process
• Xist and Tsix Two genes actively involved in inactivating an X chromosome Antagonistic roles Xi Xa Xist expression Tsix expression Xist expression Tsix expression (Lee et al., 1999)
Process
• Xist and Tsix Only genes expressed on Xi X chromosome lacking Xist gene cannot be inactivated cen Xist/Tsix in XIC
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) cen Xa Xist RNA cen Xi
Process
• Mechanism for compacting Xi (Barr body) Enzymes cause the following to occur: High levels of DNA methylation (CH 3 ) (Chadwick et al., 2003) Low levels of histone substitution of the acetyl group (CH 3 CO) for a H atom in a OH group (www.en.wikipedia.org/wiki/Acetylation)
cen Xa CH 3 CH 3 Xist RNA CH 3 CH 3 CH 3 cen CH 3 CH 3 CH 3 CH 3 CH 3 Xi
H2A H3
Process
High levels of histone H2A everywhere (deNapoles et al., 2004) High levels of histone H3 methylation (Heard et al., 2001) cen Xa cen Xi
Barrbody: Source, BIODIDAC, University of Ottawa. http://biodidac.bio.uottawa.ca
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".
Nature
434
(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 )
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 )
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 )
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 .
REFERENCES
• • • • • • http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20 101/Bio%20101%20Lectures/Genetics-%20Chromosomes/non mend.htm
Accessed on 7/13/07 http://biology.clc.uc.edu/graphics/bio105/barr.jpg
7/12/07(free image) Accessed on http://faculty.uca.edu/~johnc/Barr%20Body%20Cat.jpg.
7/12/07 Accessed on 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