Insights into interphase large-scale chromatin structure from analysis of engineered chromosome regions

A. S. Belmont, Y. Hu, P. B. Sinclair, W. Wu, Q. Bian, I. Kireev

Research output: Contribution to journalArticle

Abstract

How chromatin folds into mitotic and interphase chromosomes has remained a difficult question for many years. We have used three generations of engineered chromosome regions as a means of visualizing specific chromosome regions in live cells and cells fixed under conditions that preserve large-scale chromatin structure. Our results confirm the existence of large-scale chromatin domains and fibers formed by the folding of 10-nm and 30-nm chromatin fibers into larger, spatially distinct domains. Transcription at levels within severalfold of the levels measured for endogenous loci occur within these large-scale chromatin structures on a condensed template linearly compacted several hundred fold to 1000-fold relative to B-form DNA. However, transcriptional induction is accompanied by a severalfold decondensation of this large-scale chromatin structure that propagates hundreds of kilobases beyond the induced gene. Examination of engineered chromosome regions in mouse embryonic stem cells (ESCs) and differentiated cells suggests a surprising degree of plasticity in this large-scale chromatin structure, allowing long-range DNA interactions within the context of large-scale chromatin fibers. Recapitulation of genespecific differences in large-scale chromatin conformation and nuclear positioning using these engineered chromosome regions will facilitate identification of cis and trans determinants of interphase chromosome architecture.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalCold Spring Harbor symposia on quantitative biology
Volume75
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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