3D Chromosome Regulatory Landscape of Human Pluripotent Cells

Cell Stem Cell. 2016 Feb 4;18(2):262-75. doi: 10.1016/j.stem.2015.11.007. Epub 2015 Dec 10.

Abstract

In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Human / genetics*
  • Cohesins
  • DNA / chemistry
  • DNA / metabolism
  • Disease / genetics
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Insulator Elements / genetics
  • MicroRNAs / metabolism
  • Nucleic Acid Conformation
  • Pluripotent Stem Cells / metabolism*
  • Repressor Proteins
  • Transcription Factors / metabolism

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • MicroRNAs
  • Repressor Proteins
  • Transcription Factors
  • DNA