Xist RNA and X-Chromosome Inactivation: Mini
Lecture
Learning Outcomes
1. Define Xist RNA and its role in X-chromosome inactivation (XCI).
2. Explain dosage compensation.
3. Describe key Xist repeat domains.
4. Discuss SPEN, RBM15/WTAP and hnRNP K.
5. Understand Polycomb recruitment during XCI.
1. Introduction to Xist RNA
Xist is a long non-coding RNA that acts as the master regulator of X-chromosome inactivation.
Female mammals possess two X chromosomes whereas males possess one. XCI ensures equal
expression of X-linked genes between sexes.
2. How Xist Functions
Xist is transcribed from one X chromosome, spreads across that chromosome in cis, silences
genes and promotes formation of the Barr body. Experiments with autosomal Xist transgenes
showed that Xist alone is sufficient to trigger gene silencing.
3. The X-Inactivation Centre
The Xic contains regulators of Xist. Negative regulators include Tsix, Xite, Linx and Tsx. Positive
regulators include Jpx and Ftx.
4. Structure of Xist RNA
The A-repeat consists of about 7.5 copies of a conserved 26-nt sequence and is essential for gene
silencing. Deletion of the A-repeat severely impairs silencing.
5. Key Protein Partners
SPEN binds the A-repeat and initiates silencing. RBM15 and WTAP participate in m6A RNA
methylation. hnRNP K binds repeats B and C and recruits PRC1.
6. Polycomb Recruitment
The original model suggested direct recruitment of PRC2 by Repeat A. Proteomic studies failed to
detect PRC2 components on Xist and instead identified PRC1. The current model proposes PRC1
recruitment first, followed by PRC2.
7. Xist and Chromosome Architecture
Xist helps reorganize the inactive X chromosome into a compact structure. Proteins such as hnRNP
U, CIZ1 and SmcHD1 contribute to localization and maintenance of silencing.
Lecture
Learning Outcomes
1. Define Xist RNA and its role in X-chromosome inactivation (XCI).
2. Explain dosage compensation.
3. Describe key Xist repeat domains.
4. Discuss SPEN, RBM15/WTAP and hnRNP K.
5. Understand Polycomb recruitment during XCI.
1. Introduction to Xist RNA
Xist is a long non-coding RNA that acts as the master regulator of X-chromosome inactivation.
Female mammals possess two X chromosomes whereas males possess one. XCI ensures equal
expression of X-linked genes between sexes.
2. How Xist Functions
Xist is transcribed from one X chromosome, spreads across that chromosome in cis, silences
genes and promotes formation of the Barr body. Experiments with autosomal Xist transgenes
showed that Xist alone is sufficient to trigger gene silencing.
3. The X-Inactivation Centre
The Xic contains regulators of Xist. Negative regulators include Tsix, Xite, Linx and Tsx. Positive
regulators include Jpx and Ftx.
4. Structure of Xist RNA
The A-repeat consists of about 7.5 copies of a conserved 26-nt sequence and is essential for gene
silencing. Deletion of the A-repeat severely impairs silencing.
5. Key Protein Partners
SPEN binds the A-repeat and initiates silencing. RBM15 and WTAP participate in m6A RNA
methylation. hnRNP K binds repeats B and C and recruits PRC1.
6. Polycomb Recruitment
The original model suggested direct recruitment of PRC2 by Repeat A. Proteomic studies failed to
detect PRC2 components on Xist and instead identified PRC1. The current model proposes PRC1
recruitment first, followed by PRC2.
7. Xist and Chromosome Architecture
Xist helps reorganize the inactive X chromosome into a compact structure. Proteins such as hnRNP
U, CIZ1 and SmcHD1 contribute to localization and maintenance of silencing.
