Summer 2007 Workshop in Biology and Multimedia for High School Teachers

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

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

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

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

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 Xi Xa cen Xist RNA

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 (

cen XiXa cen Xist RNA CH 3

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

Barrbody: Source, BIODIDAC, University of Ottawa.

REFERENCES Barrbody: Source, BIODIDAC, University of Ottawa. 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 PDFFull Text PDF Carrel L, Willard H (2005). "X-inactivation profile reveals extensive variability in X-linked gene expression in females". Nature 434 (7031): PMID PMID Chadwick,B.P., Willard,H.F., (2003), Barring gene expression after XIST: maintaining faculative heterochromatin on the inactive X. j.semcdb 14, (Abstract)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, (Abstract)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, (Abstract)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, (Full Text)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, (Full Text)Full Text) Lee, J. T., (2003), X-chromosome inactivation: a multi- disciplinary approach. j.semcdb 14, (doi: /j.semcdb (Abstract)doi: /j.semcdb Lyon, M. (1961). "Gene action in the X-chromosome of the mouse (Mus musculus L.)". Nature 190: PMID PMID Lyon, M. F., (2003), The Lyon and the LINE hypothesis. j.semcdb 14, (Abstract)Abstract

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

REFERENCES /Bio%20101%20Lectures/Genetics-%20Chromosomes/non- mend.htm Accessed on 7/13/07http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%2 0101/Bio%20101%20Lectures/Genetics-%20Chromosomes/non- mend.htm Accessed on 7/12/07(free image) Accessed on 7/12/07http://faculty.uca.edu/~johnc/Barr%20Body%20Cat.jpg. Accessed 7/13/07www.whonamedit.com/doctor.cfm/2473.html Accessed 7/13/07www.biologyreference.com/Re-Se/Sex-Chromosome.html Accessed 7/12/07www.en.wikipedia.org/wiki/Acetylation