CTCF-mediated topological boundaries during development foster appropriate gene regulation

Varun Narendra, Milica Bulajié, Job Dekker, Esteban O. Mazzoni, Danny Reinberg

Research output: Contribution to journalArticle

Abstract

The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated fromits neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development.

Original languageEnglish (US)
Pages (from-to)2657-2662
Number of pages6
JournalGenes and Development
Volume30
Issue number24
DOIs
StatePublished - Dec 15 2016

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Keywords

  • CTCF
  • Chromatin and epigenetics
  • Chromosomal conformation
  • Hox gene regulation
  • Polycomb/Trithorax
  • TADs

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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