Rules governing the mechanism of epigenetic reprogramming memory.

Abstract:

AIM:Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS:We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION:Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions. The epigenetic-memory molecular origin is the expression of source-cell transcription factors protecting hypomethylated SMSs in euchromatin from de novo methylation, keeping source-cell lineage-specific loci in induced pluripotent stem (iPS) cells incompletely silenced. Sites in lineage-specific genes of different-from-those-of-the-source-cell lineages remain hypermethylated in heterochromatin regions becoming permanently silenced. SMSs cause differential expression between iPS cells and embryonic stem cells through two mechanisms: 'epigenetic/expression memory rule', the DNA unreprogramming methylation status coupled with chromatin states induces differentially expressed genes. 'Imprinting control', the change of DNA methylation status in imprinting control regions induces differential expression of imprinted genes.

journal_name

Epigenomics

journal_title

Epigenomics

authors

Luu PL,Gerovska D,Schöler HR,Araúzo-Bravo MJ

doi

10.2217/epi-2017-0098

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

149-174

issue

2

eissn

1750-1911

issn

1750-192X

journal_volume

10

pub_type

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