X-Inactivation
In every female cell one of the two X chromosomes is silenced by XIST + DNA methylation. It's random — that's why women are mosaics.
“The goal is not to methylate everything. The goal is to regulate the right genes, in the right tissues, at the right time, at the right intensity.”
Tissue mosaic (1 cell = 1 choice)
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Letter shown = active XMaternal silenced: 50% · Paternal silenced: 50%
XIST
lncRNA expressed from the X to be inactivated. It 'paints' the chromosome, recruits repressive complexes (PRC2, H3K27me3) and drives promoter DNA methylation.
Barr body
The inactive X condenses into heterochromatin visible under the microscope. Maintained by DNMT1 at every cell division.
That's why calico cats are only female — each cell 'picks' one X and that paints the coat as a mosaic.