High-resolution Xist binding maps reveal two-step

spreading during X-chromosome inactivation

Logan McColl Biochemistry AC

Matthew D. Simon1,2*, Stefan F. Pinter1,3*, Rui Fang2*, Kavitha Sarma1,3, Michael Rutenberg Schoenberg2,
Sarah K. Bowman1, Barry A. Kesner1,3, Verena K. Maier1,3, Robert E. Kingston1 & Jeannie T. Lee1,3
1Department

of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114,
USA. 2Department of Molecular Biophysics and Biochemistry, and Chemical Biology Institute, Yale University, West Haven, Connecticut 06516, USA. 3Howard
Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
*These authors contributed equally to this work.

General Overview of X-Inactivation:

When an embryonic cell begins to replicate, a randomly *Xist recruits Polycomb repressive complex 2
selected X chromosome is condensed into a Barr body
(PRC2) to the X-inactivation center (XIC).
which ensures both chromosomes are not expressed (in
females).
Xist (long non-coding) RNA coats the future inactive X
chromosome during inactivation.

Main claims made by the paper:

Xist repression follows a step mechanism (de novo) in female cells
undergoing X-Chromosome Inactivation.
The most active genes on the X chromosome which is to be silenced
are repressed first (first stage).
After the repression of the most active genes Xist then spreads to
gene poor domains (second stage).
Once this second stage is complete, any further maintenance steps
occur at the same time i.e. active gene sites and non-active repeats
will be targeted by Xist at the same rate.

Sources
Nature : High-resolution Xist binding maps reveal two-step spreading during X-chromosome
inactivation by Matthew D. Simon1,2*, Stefan F. Pinter1,3*, Rui Fang2*, Kavitha Sarma1,3, Michael
Rutenberg-Schoenberg2, Sarah K. Bowman1, Barry A. Kesner1,3, Verena K. Maier1,3, Robert E.
Kingston1 & Jeannie T. Lee1,3
Molecular Biology of the Cell 5th edition, Chapter 7: Control of Gene Expression, by Bruce Alberts,
Alexander Johnson, Julian Lewis, Martin Ragg, Keith Roberts, and Peter Walter.
Dr. Palmiters Lecture Slides
PNAS : The genomic binding sites of a noncoding RNA by Matthew D. Simona, Charlotte I.
Wangb, Peter V. Kharchenkoc, Jason A. Westa, Brad A. Chapmana, Artyom A. Alekseyenkob, Mark L.
Borowskya, Mitzi I. Kurodab, and Robert E. Kingstona,1
NCBI : Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations by
Stefan F. Pinter,1,2,3 Ruslan I. Sadreyev,1,2,3 Eda Yildirim,1,2,3 Yesu Jeon,1,2,3 Toshiro K.
Ohsumi,2,3 Mark Borowsky,2,3 and Jeannie T. Lee1,2,3,4
NCBI : Intersection of the RNA interference and X-inactivation pathways Ogawa Y1, Sun BK, Lee
JT
PNAS : Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA
localization to the X chromosome by Kavitha Sarma,a Pierre Levasseur,b Alexander
Aristarkhov,b and Jeannie T. Leea,1