Large-scale chromatin structure-function relationships during the cell cycle and development: Insights from replication timing

Vishnu Dileep, Juan Carlos Rivera-Mulia, Jiao Sima, David M. Gilbert

Research output: Chapter in Book/Report/Conference proceedingChapter

33 Scopus citations

Abstract

Chromosome architecture has received a lot of attention since the recent development of genome-scale methods to measure chromatin interactions (Hi-C), enabling the first sequence-based models of chromosome tertiary structure. A view has emerged of chromosomes as a string of structural units (topologically associating domains; TADs) whose boundaries persist through the cell cycle and development. TADs with similar chromatin states tend to aggregate, forming spatially segregated chromatin compartments. However, high-resolution Hi-C has revealed substructure within TADs (subTADs) that poses a challenge for models that attribute significance to structural units at any given scale. More than 20 years ago, the DNA replication field independently identified stable structural (and functional) units of chromosomes (replication foci) as well as spatially segregated chromatin compartments (early and late foci), but lacked the means to link these units to genomic map units. Genome-wide studies of replication timing (RT) have now merged these two disciplines by identifying individual units of replication regulation (replication domains; RDs) that correspond to TADs and are arranged in 3D to form spatiotemporally segregated subnuclear compartments. Furthermore, classifying RDs/TADs by their constitutive versus developmentally regulated RT has revealed distinct classes of chromatin organization, providing unexpected insight into the relationship between large-scale chromosome structure and function.
Original languageEnglish (US)
Title of host publicationCold Spring Harbor Symposia on Quantitative Biology
PublisherCold Spring Harbor Laboratory Press
Pages53-63
Number of pages11
ISBN (Print)9781621821472
DOIs
StatePublished - 2016

Publication series

NameCold Spring Harbor Symposia on Quantitative Biology
Volume80

Fingerprint Dive into the research topics of 'Large-scale chromatin structure-function relationships during the cell cycle and development: Insights from replication timing'. Together they form a unique fingerprint.

Cite this