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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 - PowerPoint PPT Presentation
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• 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.
History• Murray L. Barr and E. G. Bertram
1949
Dark, drumstick-shaped masses in nuclei of nerve cells
Pattern only seen in cats
www.whonamedit.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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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 - 21kAccessed on July 12, 2007. Courtsey of Michael J. Gregory, Ph.D.
Process• X inactivation center (XIC)
Near centromere
Contains 12 genes7 genes code for proteins5 genes code for untranslated RNA
(Rougeulle et al., 2003) cen
XIC
Process• Xist and Tsix
Two genes actively involved in inactivating an X chromosomeAntagonistic roles
Xi Xist expression Tsix expression
Xa 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 Xi
Xacen
Xist RNA
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)
cen Xi
Xacen
Xist RNA
CH3 CH3 CH3
CH3 CH3 CH3
CH3
CH3
CH3
CH3
Process High levels of histone H2A everywhere (deNapoles et al., 2004)
High levels of histone H3 methylation (Heard et al., 2001)
Xacen
cen Xi
H2A
H3
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 ProgramAt Harvard University’s Department of Molecular & Cellular Biologywith the graphics.
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