BMCB625: noncoding RNA (Xist)

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BMCB625 Advanced Topics in Molecular Biology

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(Homework) Questions

Jon

If I remember correctly we were taught (in CON663) human X inactivation is random, whereas in mouse, X inactivation occurs on the paternally derived X chromosome. Is this wrong (am I wrong)? How do the authors simulate this "human" (random) model?

  • It is thought that the X paternal (Xp) inactivation may occur though a resistance imprint on the X maternal (Xm); this imprint inhibits Xm from being inactivated. Thus paternal Xist leads to silencing of Xp.
  • "The paternal X chromosome is initially inactivated in all cells of cleavage-stage embryos and then selectively reactivated in the subset of cells that will form the embryo, with random X inactivation occurring thereafter."

Developmental X-inactivation

  • After the blastocyst is formed the Inner cell mass (ICM) looses the Xp Xist RNA coating and histone modifications and Xp is reactivated, followed by random X inactivation.
  • Why do you think this process occurs? What is the evolutionary advantage?
    • Perhaps an artifact of evolution?
    • A carryover effect from MSCI (silencing of X&Y in male germ line -sperm cells).


  1. Heard E. . pmid:15145348. PubMed HubMed [1]

Why is dosage compensation important? What genes are on the X chromosome that cause problems when you have gene duplication?


Chris

  1. How do Chaumeil, et al., track a "single species" of mRNA transcripts?
  2. How to they demonstrate the absence of transcription? What is a major drawback to this method? Do they truly demonstrate "absence of transcription?"

--Chris 22:22, 23 April 2007 (EDT)


Mahta

Q1. How do you think the Xist transcript is able to exclude RNA Pol II and other transcription components from a "defined" region? How would you go about testing your hypothesis?

Q2. In relation to Q1 - what do you think the Xist domain is comprised of?


Larry

  1. What approach do the authors take in order to resolve the apparent contradition of early exclusion of transcription machinery within 1-2 days and other reports showing that X-linked gene repression only begins after 2 days of differentiation?
  1. What possible role(s) might the jarid1c gene play that would excuse it from full inactivation?

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