Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding

Nat Commun. 2020 May 25;11(1):2606. doi: 10.1038/s41467-020-16394-3.

Abstract

Nucleoporin proteins (Nups) have been proposed to mediate spatial and temporal chromatin organization during gene regulation. Nevertheless, the molecular mechanisms in mammalian cells are not well understood. Here, we report that Nucleoporin 153 (NUP153) interacts with the chromatin architectural proteins, CTCF and cohesin, and mediates their binding across cis-regulatory elements and TAD boundaries in mouse embryonic stem (ES) cells. NUP153 depletion results in altered CTCF and cohesin binding and differential gene expression - specifically at the bivalent developmental genes. To investigate the molecular mechanism, we utilize epidermal growth factor (EGF)-inducible immediate early genes (IEGs). We find that NUP153 controls CTCF and cohesin binding at the cis-regulatory elements and POL II pausing during the basal state. Furthermore, efficient IEG transcription relies on NUP153. We propose that NUP153 links the nuclear pore complex (NPC) to chromatin architecture allowing genes that are poised to respond rapidly to developmental cues to be properly modulated.

Publication types

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

MeSH terms

  • Animals
  • CCCTC-Binding Factor / chemistry
  • CCCTC-Binding Factor / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Genes, Immediate-Early
  • HeLa Cells
  • Humans
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • Nuclear Pore / metabolism
  • Nuclear Pore Complex Proteins / deficiency
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • RNA Polymerase II / metabolism
  • Regulatory Elements, Transcriptional

Substances

  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Ctcf protein, mouse
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • Nup153 protein, mouse
  • cohesins
  • RNA Polymerase II