X Chromosome Activation

Question 1

Sex determination

Answer 1

Eutherian mammals = X and Y determinants
Female = XX. Large, many genes
Males = XY. Smaller, few genes

Question 2

Describe Barr bodies

Answer 2

Dark areas at edge of nuclei cells
Proposed they are condensed chromatin from inactive X chromsome
Inactivation spreads from unique locus on X

Question 3

Xic =

Answer 3

X-inactivation centre

Locus inactivation spreads form on X

Question 4

No. Of Barr bodies normal female

Answer 4

1

Question 5

No. Of Barr bodies normal male

Answer 5

0

Question 6

No. Of Barr bodies XXY

Answer 6

Male Klinefelter syndrome

1

Question 7

No. Of Barr bodies XXX

Answer 7

Normal female

2

Question 8

No. Of Barr bodies XO

Answer 8

Female Turner syndrome

0

Question 9

Cat patterning and inactive X chromosome

Answer 9

Male cats have X with either orange or black allele = no competition
Female have either black, orange or mosaic
both X’s the homozygous doesnt matter which silenced
If heterozygous then orange dominant
Can cause activation of random cells and end up part orange and black = why most tortoiseshell cats are female

Question 10

Anhidrotic ectodermal dysplasia in humans

Answer 10

Mutation in X chromosome
Males = inherit the mutation
Females = could have mosaics depending on which chromosome activated in each cell
Symptoms:
- lack of sweat glands = males completely, females mosaicism
- sparse hair
-malformed teeth

Question 11

What happens when x inactivation isn’t complete?

Answer 11

Many genes escape inactivation are present in regions that contain genes also present in Y chromosome
Pseudoautosomal regions present in 2 copies for either sex = need both for normal funcitons or haploinsufficent
Explains defects in humans wiht abnormal X numbers e.g. XXY
X inactivation should eliminate affects but the non-silenced genes still affects

Question 12

Describe Klinefelter syndrome

Answer 12

Extra X in males = XXY
Symptoms:
- small testes (reduced testosterone)
- Learning difficulties 
- infertility 
Additional x variants increase severity 
Can be treated with testosterone supplements in early development but doesnt cure 
Some symptoms develop pre-birth

Question 13

Describe turner syndrome

Answer 13

Missing or disrupted X in females = XO
Many genes haploinsufficient without both X’s
All genes responsible not yet indentified 
Some symptoms include:
- Poor breast development 
- no menstruation 
- low hairline 
- brown spots (nevi)

Question 14

Xi

Answer 14

Inactivated chromsome

Question 15

Xa

Answer 15

Activated chromosme

Question 16

Xist

Answer 16

X inactivation specific transcript

Question 17

Mechanism of x inactivation.

Answer 17

Begins in Xic
Produces RNA transcript for Xist
Xist in somatic cells only expressed in Xi
Essential for Xinactivaiton
in interphase nuclei Xist colocalises with Barr body
Stabilisation of Xist RNA mediates initiation of X inactivation
In each cell one chromosome expresses Xist - if more than one X it will inactivate as many as needed until 1 x left in
methylation locks in silencing. The more silenced the harder to reverse.

Question 18

What are the 2 models for counting/sensing X chromosomes

Answer 18

1. Protein expression occurs in X chromosomes. the protein binds to the X and acts as a promoter for Xist expression. Cooperative binding so there needs to be enough of it. Xist expression then causes chromosome to be silenced
2. Autosomal factor binds to X chromosome and prevents proteins binding. The protein binds to a different x chromosome and silences it.

Both allow counting and make sure one silent, one active

Question 19

Describe RNF12

Answer 19

Located 500bp from xist
Has ubiquitin ligase properties = high levels degrade xist repressor in embryonic somatic cells. A trans activating factor
Breaking down repressor means Xist active and begins to silence
As RNF12 nearby it gets silenced = reduces concentration of repressor
Causes one active and one silenced X chromsome
If XXX RNF12 repressor produced to level where 2 X’s silenced

Question 20

Describe Tsix

Answer 20

Important to inactivation 3’ of Xist 
Loci that prevents Xist transcription 
On equivalent position to Xist on other strand = antisense transcription across promoter 
Changes chromatin structure 
Complex and not fully understood yet

Question 21

Regulation of Xist by Tsix

Answer 21

Tsix regulated by long range cis active elements, pluipotency factors and Xite
Deletions skew silencing
Transcribing Tsix prevents machinery from transcribing Xist

Question 22

Name other factors that regulate Tsix, RNF12 and Xist

Answer 22

Oct 4 = cell differentiation, producing stem cells
PRDM14 = developmental genes
SOX = differentiation
REX = imprinting

Question 23

Name histone structures that chnage with inactivation

Answer 23

Trimethylates lysine 27 histone 3
Ubiquinates histone 2
Hypoacetylates histone 4