Dynamic plasticity of large-scale chromatin structure revealed by self-assembly of engineered chromosome regions

Paul Sinclair, Qian Bian, Matt Plutz, Edith Heard, Andrew S. Belmont

Research output: Contribution to journalArticle

Abstract

Interphase chromatin compaction well above the 30-nm fiber is well documented, but the structural motifs underlying this level of chromatin folding remain unknown. Taking a reductionist approach, we analyzed in mouse embryonic stem (ES) cells and ES-derived fibroblasts and erythroblasts the folding of 10-160-megabase pair engineered chromosome regions consisting of tandem repeats of bacterial artificial chromosomes (BACs) containing ∼200 kilobases of mammalian genomic DNA tagged with lac operator (LacO) arrays. Unexpectedly, linear mitotic and interphase chromatid regions formed from noncontiguously folded DNA topologies. Particularly, in ES cells, these model chromosome regions self-organized with distant sequences segregating into functionally distinct, compact domains. Transcriptionally active and histone H3K27me3-modified regions positioned toward the engineered chromosome subterritory exterior, with LacO repeats and the BAC vector backbone localizing within an H3K9me3, HP1-enriched core. Differential compaction of Dhfr and α- and β-globin transgenes was super-imposed on dramatic, lineage-specific reorganization of large-scale chromatin folding, demonstrating a surprising plasticity of large-scale chromatin organization.

Original languageEnglish (US)
Pages (from-to)761-776
Number of pages16
JournalJournal of Cell Biology
Volume190
Issue number5
DOIs
StatePublished - Sep 6 2010

ASJC Scopus subject areas

  • Cell Biology

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