Extra reading Flashcards
What is dosage compensation?
Process by which organisms equalise the expression from the X chromosome in males and females
What is X inactivation? (2)
- Inactivation of an X chromosome in any cell in early female embryo is random and permanent
- Means that female mammals are mosaic for X inactivation
What is Xic? (2)
- The X inactivation centre
- Cis-acting master switch locus for initiation of X inactivation
What are the components of the Xic? (4)
- Xist
- Tsix
- Rex1
- Rnf12
What is the function of Xist? (2)
- Non-coding RNA which decorates the entire length of the X chromosome from which it is transcribed
- Prevention of diffusion to the other X chromosome is not understood
What is the function of Tsix? (2)
- Complementary to Xist RNA
- Expression of one inactivates the other
How does Xist cause X inactivation?
The first chromosome to accumulate above a threshold amount of Xist is the one that is inactivated
What is the function of Rnf12? (3)
- Ubiquitin ligase encoded by Xic locus
- Degrades Rex1
- More Rnf12 production means more Xist production and less Tsix production
What is the function of Rex1? (2)
- Autosomally derived protein
- Transcriptional repressor of Xist RNA
How is X inactivation propagated and maintained beyond the Xic? (3)
- YY1 transcription factor binds to Xist RNA
- Triggers further accumulation of YY1 binding to Xist with hnRNPU RNA binding protein
- Complex spreads along the chromosome to allow decoration with Xist
What are the events which follow Xist inactivation of the X chromosome? (10)
- Xist decorates the inactive X
- Core histone acetylation is decreased
- Core histone H3K4 methylation is decreased
- Core histone H3K27 methylation is increased (polycomb)
- Core histone H2A ubiquitination of lysine 119 is increased (H2AK119Ub)
- PRC2 and PRC1 binding is increased
- H3K9 methylation is increased
- HP1alpha binding is increased
- CpG DNA methylation is increased
- All causes condensation of inactive X into the Barr body which can’t be transcribed
How is dosage compensation achieved in mammals? (2)
- Xist RNA decorates the X from which it is transcribed and recruits YY1 and hnRNPU
- 1 X is silenced by decreasing H3K4 methylation and histone acetylation and promoting H3K27 and H3K9 methylation , polycomb complex, HP1alpha recruitment and DNA methylation
What is the function of piRNA?
Cleaves products of transposons in germ cells
What causes fragile X syndrome? (3)
- CGG trinucleotide expansion in the FMR1 gene suppresses its expression and reduces abundance of the fragile X mental retardation protein (FMRP)
- FMRP regulates neuronal connectivity and plasticity
- Causes mental impairment and autism in humans
What is the nature of FMRP?
miRNA binding protein