Affordable Access

deepdyve-link
Publisher Website

One protein to rule them all: The role of CCCTC-binding factor in shaping human genome in health and disease.

Authors
  • Lazniewski, Michal1
  • Dawson, Wayne K2
  • Rusek, Anna Maria3
  • Plewczynski, Dariusz4
  • 1 Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland; Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland. , (Poland)
  • 2 Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland; Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 103-8657, Japan. , (Japan)
  • 3 Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland; Clinical Molecular Biology Department, Medical University of Bialystok, Bialystok, Poland. , (Poland)
  • 4 Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland; Centre for Innovative Research, Medical University of Bialystok, Bialystok, Poland; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland. Electronic address: [email protected] , (Poland)
Type
Published Article
Journal
Seminars in Cell and Developmental Biology
Publisher
Elsevier
Publication Date
Jun 01, 2019
Volume
90
Pages
114–127
Identifiers
DOI: 10.1016/j.semcdb.2018.08.003
PMID: 30096365
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The eukaryotic genome, constituting several billion base pairs, must be contracted to fit within the volume of a nucleus where the diameter is on the scale of μm. The 3D structure and packing of such a long sequence cannot be left to pure chance, as DNA must be efficiently used for its primary roles as a matrix for transcription and replication. In recent years, methods like chromatin conformation capture (including 3C, 4C, Hi-C, ChIA-PET and Multi-ChIA) and optical microscopy have advanced substantially and have shed new light on how eukaryotic genomes are hierarchically organized; first into 10-nm fiber, next into DNA loops, topologically associated domains and finally into interphase or mitotic chromosomes. This knowledge has allowed us to revise our understanding regarding the mechanisms governing the process of DNA organization. Mounting experimental evidence suggests that the key element in the formation of loops is the binding of the CCCTC-binding factor (CTCF) to DNA; a protein that can be referred to as the chief organizer of the genome. However, CTCF does not work alone but in cooperation with other proteins, such as cohesin or Yin Yang 1 (YY1). In this short review, we briefly describe our current understanding of the structure of eukaryotic genomes, how they are established and how the formation of DNA loops can influence gene expression. We discuss the recent discoveries describing the 3D structure of the CTCF-DNA complex and the role of CTCF in establishing genome structure. Finally, we briefly explain how various genetic disorders might arise as a consequence of mutations in the CTCF target sequence or alteration of genomic imprinting. Copyright © 2018 Elsevier Ltd. All rights reserved.

Report this publication

Statistics

Seen <100 times