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.
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
Qui ckT ime™ and a
T IFF (Uncompres sed) decompres sor
are needed to s ee 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 - 21k
Accessed on July 12, 2007. Courtsey of M ichael 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   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
Xa
cen
Xi
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)
Xa
cen
Xist RNA
CH3
CH3
CH3 CH3
Xi
cen
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)
cen
Xa
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 XChromosome 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, 400404. (Full Text)
• Lee, J. T., (2003), X-chromosome inactivation: a multidisciplinary 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/nonmend.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