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Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription.

Abstract：

:The remarkable stability of gene expression in somatic cells is exemplified by the way memory of an active gene state is retained when an endoderm cell nucleus is transplanted to an enucleated egg. Here we analyse the mechanism of a similar example of epigenetic memory. We find that memory can persist through 24 cell divisions in the absence of transcription and applies to the expression of the myogenic gene MyoD in non-muscle cell lineages of nuclear transplant embryos. We show that memory is not explained by the methylation of promoter DNA. However, we demonstrate that epigenetic memory correlates with the association of histone H3.3 with the MyoD promoter in embryos that display memory but not in those where memory has been lost. The association of a mutated histone H3.3 (H3.3 E4, which lacks the methylatable H3.3 lysine 4) with promoter DNA eliminates memory, indicating a requirement of H3.3 K4 for memory. We also show that overexpression of H3.3 can enhance memory in transplanted nuclei. We therefore conclude that the association of histone H3.3 with the MyoD promoter makes a necessary contribution to this example of memory. Hence, we suggest that epigenetic memory helps to stabilize gene expression in normal development; it might also help to account for the inefficient reprogramming in some transplanted nuclei.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Ng RK,Gurdon JB

doi

10.1038/ncb1674

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

102-9

issue

1

eissn

1465-7392

issn

1476-4679

pii

ncb1674

journal_volume

10

pub_type

杂志文章

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