• 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