47. Irrespective of the chromosomal configuration, a single X chromosome remains active in all diploid human somatic cell lines. Which one of the following mechanisms best accounts for the above phenomenon?
(1) A maternally inherited X—chromosome is developmentally programmed to remain active by avoiding DNA methylation.
(2) Chromosome specific expression and binding of rox1 to one of the X-chromosomes protects it from Xist mediated silencing.
(3) The T-six gene produces just enough of the Xist antisense RNA to block one Xic locus.
(4) A cell produces just enough of the blocking factor to block one Xic locus.
Introduction
In female mammals, dosage compensation is achieved by X chromosome inactivation (XCI), where one of the two X chromosomes is transcriptionally silenced to equalize gene expression with XY males. Despite the presence of two X chromosomes, only a single X remains active in each diploid somatic cell. Understanding the molecular basis of this selective activation is fundamental to genetics and epigenetics.
Overview of X Chromosome Inactivation
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XCI is controlled by the X-inactivation center (Xic), a locus on the X chromosome that contains key regulatory genes including XIST, a long non-coding RNA essential for initiating silencing.
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The process involves counting the number of X chromosomes, choosing one to remain active, and silencing the other(s).
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Once established, the inactive X is maintained through cell divisions by epigenetic mechanisms such as DNA methylation and heterochromatin formation.
Mechanism Ensuring a Single Active X Chromosome
Among several models proposed, a widely accepted mechanism is that:
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The cell produces a limited amount of a blocking factor that binds to the X-inactivation center (Xic) on one X chromosome.
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This blocking factor prevents XIST expression on that chromosome, thereby protecting it from inactivation.
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The other X chromosome, lacking sufficient blocking factor binding, expresses XIST and becomes inactivated.
This mechanism ensures that only one X chromosome remains active regardless of the total number of X chromosomes present.
Evaluating the Options
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Maternally inherited X chromosome programmed to avoid DNA methylation:
Not supported; XCI is random in humans and not strictly imprinted as in some marsupials. -
Chromosome-specific expression and binding of rox1 to protect one X chromosome:
roX1 is a Drosophila-specific RNA involved in dosage compensation, not relevant in mammals. -
T-six gene producing antisense RNA to block one Xic locus:
Tsix is involved in regulating Xist but does not fully explain the single active X chromosome mechanism. -
Cell produces just enough blocking factor to block one Xic locus:
This aligns with current understanding: a limited blocking factor binds one Xic, keeping that X active.
Conclusion
The best explanation for why a single X chromosome remains active in human somatic cells is:
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A cell produces a limiting amount of a blocking factor that binds to one X-inactivation center, preventing its inactivation and ensuring only one X chromosome remains active.
Answer:
The correct option is (4) A cell produces just enough of the blocking factor to block one Xic locus.
