Q18.3-3CC.

Question

Inactivation of one of the X chromosomes in female mammals involves IncRNA called XIST RNA, mentioned in this section and in Concept 15.2. Describe transcription and binding of XIST RNA, then suggest a model for how it initiates Barr body formation.

Step-by-Step Solution

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Answer

The IncRNA is synthesized from XIST (X-inactive specific transcript) gene located on the X-chromosome. The IncRNA binds to the X-chromosome and leads to the formation of heterochromatin. 

 

The model suggests that XIST RNA induces chemical modifications of the DNA and proteins that cause the X chromosome to condense into Barr bodies.

1Step 1: Inactivation of the X chromosome

Human females possess two X chromosomes, whereas males possess one X and one Y chromosome. However, one X chromosome is inactivated in females during early embryonic development.


As a result, both males and females have an equal amount of X-genes. This process is called X-inactivation, which is caused by lncRNA (long non-coding RNAs).


2Step 2: Explanation for transcription and binding of XIST RNA

IncRNA is non-coding RNAs that are up to a thousand nucleotides in length. This mRNA transcript is synthesized from the XIST gene present on the X-chromosome to be inactivated.


lncRNA binds and coats the X-chromosome from which it is synthesized. The binding causes the condensation of the X chromosome into heterochromatin.


3Step 3: Formation of Barr body

The inactive X-chromosome in females is the Barr body. It appears as a dense body near the periphery of the cell nucleus. The model suggests that IncRNA on binding to the X-chromosome recruits enzymes on the chromosome involved in chromatin formation. 

 

The enzyme causes chemical modification of DNA and histones, such as adding a methyl group to the DNA nucleotides. This causes the compaction of DNA and leads to the formation of the Barr body. 

 

As a result, genes on the X-chromosome are silenced, leading to the X chromosome's inactivation.