Sex determination in mammals and drosophila 2 Flashcards
What is the first step in x inactivation?
Xist initiates gene silencing
Which enzyme does Xist activate?
Histone deacetylase
What is the effect of removing acetyl groups from histones?
Reduced translation
What happens in X inactivation after activation of histone deacetylase?
Polycomb protein activated
How is polycomb protein involved in X inactivation?
Xist binds to the polycomb repressor complex and causes methylation of H3K27
What is the third stage of X inactivation?
DNA methylation on CPG islands by DNA methyltransferase
How does a cell count the number of X chromosomes it has?
RNF12 targets REX1 TF. REX1 inhibits Xist. More RNF12=more Xist. RNF12 is on X chromosome so more RNF12=more X inactivation
What happens upon ectopic RNF12 expression?
Xist is expressed in male cells
What sex do XX flies develop into?
Females
What sex do XY flies develop in?
males
Main observable difference between female and male drosophila?
Males have a dark tip at the end of the abdomen
What sex do XO flies develop into?
Males, but they are sterile
Which sex chromosome pair shows a difference in phenotypic sex between humans and drosophila?
XO (human female, drosophila male) and XXY (human male, drosophila female)
What determines sex in drosophila?
The ratio of X chromosomes to autosomes
What is the sex of a drosophila organism that has X:AA (0.5)?
Male
What is the sex of a drosophila organism that has XX:AA (1)?
Female
What is the sex of a drosophila organism that has XX:AAA (0.66)?
It will develop with both male and female characteristics–> intersex
What are gynandromorphs?
Animals composed partly of XX cells and partly of XO cells
How are gynandromorphs generated?
XX embryos that loses one of the X chromosomes early in embryogenesis–> the organism is half XX and half XO if the loss occurs at the first division
Difference in sex determination between mammals and drosophila?
In mammals the sex based differentiation depends upon hormones secreted by gonads, in the fly the sex based differentiation depend on the chromosomal sex of the cells that differentiate
What is the Sxl (sex lethal) gene required for in drosophila?
Female development
What happens to a female fly that has a loss of function mutation in the Sxl gene?
It is lethal but only to the female
What type of mutations in the Sxl gene are lethal to males?
Gain of function mutations
In what state must the Sxl gene be to promote male development?
Inactive
In what state must the Sxl gene be to promote female development?
Active
What female specific effect does mutations in sisterless-a and sisterless-b have?
They are lethal
What do the sisterless genes encode?
Basic helix-loop-helix (bHLH) proteins
What type of protein (their role) are bHLH proteins?
TFs, DNA binding motifs
Which chromosomes has the sis-a and sis-b genes?
X-chromosome
How much sis-a and sis-b protein do XX cells make compared to XY or XO cells?
Twice as much
What happens if sis proteins homodimerises?
It can bind DNA and act as a TF
What is a target of a sis protein homodimer?
Sxl, activating Sx
What happens if a sis protein heterodimerises with an autosomal bHLH?
They result in inactive complexes
Why are sis proteins more likely to form homodimers in XX individuals?
There is a higher ratio of sis bHLH proteins to autosomal bHLH proteins
What happens if more sis bHLH homodimers form?
The Sxl gene is turned on, so that cell is female
What process does the Sxl gene regulate?
Splicing of mRNA
What is the RRM type proteins that Sxl contains?
RNA binding proteins
Which sequences does Sxl recognise?
Sequences with long Poly U stretches interrupter by guanosines
Where are the Sxl recognition sequences located?
In introns flanking the third exon
What specifically does Sxl bind to?
SPF45
What effect does Sxl binding have on SPF45?
SPF45 is inactivated
What effect does Sxl have on mature mRNA formation?
Exon 2 is fused with Exon 4 instead of exon 3 being in the middle–> female development
