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Chromatin

Defining heterochromatin

Nature Reviews Molecular Cell Biology volume 13, pages 684–685 (2012)Cite this article

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They observed that both PAX3-deficient primary mouse embryonic fibroblasts (MEFs) and Pax3-null mouse embryonic stem (ES) cells showed disrupted heterochromatin, and that the numbers of major satellite transcripts were increased in PAX3-deficient primary MEFs, indicating a role for PAX3 in maintaining heterochromatin. Next, they showed that PAX3 binds to the major satellite consensus sequence via its homeodomain in vitro and represses the transcription of double-stranded RNA from these regions.

The levels of trimethylated Lys9 on histone H3 (H3K9me3), which is associated with constitutive heterochromatin, were decreased in PAX3-deficient cells. However, PAX9 allowed recovery of H3K9me3 at pericentric chromatin in PAX3-deficient immortilized MEFs, suggesting that PAX3 and PAX9 act redundantly in heterochromatin maintenance. Short hairpin RNA-mediated knockdown of either PAX3 or PAX9 in wild-type immortalized MEFs revealed that PAX3 is the major transcription factor that maintains heterochromatin, as its loss had stronger effects on H3K9me3 temporary dispersion and derepression of major satellite transcripts than loss of PAX9.

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ORIGINAL RESEARCH PAPER

  1. Bulut-Karslioglu A. et al. A transcription factor-based mechanism for mouse heterochromatin formation. Nature Struct. Mol. Biol. 16 Sep 2012 (doi:10.1038/nsmb.2382)

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  1. Andrea Du Toit
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Du Toit, A. Defining heterochromatin. Nat Rev Mol Cell Biol 13, 684–685 (2012). https://doi.org/10.1038/nrm3450

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