Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells

Bo Wen, Hao Wu, Yoichi Shinkai, Rafael A. Irizarry, Andrew P. Feinberg

Research output: Contribution to journalArticlepeer-review

Abstract

Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only ∼4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, ∼46% in liver and ∼10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.

Original languageEnglish (US)
Pages (from-to)246-250
Number of pages5
JournalNature genetics
Volume41
Issue number2
DOIs
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells'. Together they form a unique fingerprint.

Cite this