Startseite Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
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Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells

  • Laura P. O'Neill , Hugh T. Spotswood , Milan Fernando und Bryan M. Turner
Veröffentlicht/Copyright: 27. März 2008
Biological Chemistry
Aus der Zeitschrift Band 389 Heft 4

Abstract

Silencing of genes on one of the two female X chromosomes early in development helps balance expression of X-linked genes between XX females and XY males and involves chromosome-wide changes in histone variants and modifications. Mouse female embryonic stem (ES) cells have two active Xs, one of which is silenced on differentiation, and provide a powerful model for studying the dynamics of X inactivation. Here, we use immunofluorescence microscopy of metaphase chromosomes to study changes in H3 mono-, di- or tri-methylated at lysine 4 (H3K4me1, -2 or -3) on the inactivating X (Xi) in female ES cells. H3K4me3 is absent from Xi in approximately 25% of chromosome spreads by day 2 of differentiation and in 40–50% of spreads by days 4–6, making it one of the earliest detectable changes on Xi. In contrast, loss of H3K4me2 occurs 1–2 days later, when histone acetylation also diminishes. Remarkably, H3K4me1 is depleted on both (active) X chromosomes in undifferentiated female ES cells, and on the single X in males, and remains depleted on Xi. Consistent with this, chromatin immunoprecipitation reveals differentiation-related reductions in H3K4me2 and H3K4me3 at the promoter regions of genes undergoing X-inactivation in female ES cells, but no comparable change in H3K4me1.


Corresponding author

Received: 2007-11-1
Accepted: 2008-1-6
Published Online: 2008-03-27
Published in Print: 2008-04-01

©2008 by Walter de Gruyter Berlin New York

Heruntergeladen am 3.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/BC.2008.046/pdf
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