X-Chromosome Inactivation: Xist & the Barr Body

Founder Cohort

Founder cells at XCI 14

Maternal-X skew 50%

Xist spreading speed 1.0×

Tissue Mosaic

Maternal X active Paternal X active

Maternal-active cells

50%

Paternal-active cells

50%

Clonal patches (founders)

Barr-body condensation (inset)

How it works

Every female mammalian cell carries two X chromosomes, but only one may stay transcriptionally active — a dosage-compensation rule discovered by Mary Lyon (1961). Early in embryogenesis, each epiblast cell independently and randomly silences one X:

P(maternal X active) = p         (the skew probability)
P(paternal X active) = 1 − p
choice is made once per progenitor cell, then is CLONALLY inherited
by every descendant → patches, not single-cell speckle

The silenced chromosome is coated in cis by Xist, a long non-coding RNA transcribed from the X-inactivation centre (XIC). Xist spreads outward along the chromosome and recruits PRC2 (depositing H3K27me3), DNA methyltransferases and histone deacetylases, converting open euchromatin into dense, transcriptionally silent heterochromatin — the compact Barr body visible in interphase nuclei.

Expected clonal patch size follows directly from how many progenitor cells existed at the moment of inactivation:

patch area ≈ tissue area / F        (F = founder/progenitor cells)

Founder cells — fewer founders at the time of XCI ⇒ each clone expands further ⇒ larger, coarser patches (this is the same math behind calico-cat fur patches and human skewed-XCI disease mosaics).
Maternal-X skew — biases the coin flip each founder makes; extreme skew (near 0% or 100%) models pathological skewed XCI seen in X-linked carrier females.
Xist spreading speed — how fast the inset chromosome's Xist coating (small dots) sweeps from the XIC outward and the chromatin condenses into a Barr body; the wave starts at one end and both the RNA coating and the compaction lag behind it, exactly as ChIP-seq spreading profiles show in real cells.

Real-world relevance: this random, clonally-fixed silencing is why carrier females of X-linked disorders (e.g. red-green color blindness, some forms of hemophilia) show partial, patchy phenotypes instead of an all-or-nothing outcome — and why calico/tortoiseshell cat coats are visual proof of X-inactivation mosaicism.

Active X (open chromatin) Xist RNA coating Silenced X → Barr body

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