Article

Chromosome Research

, Volume 14, Issue 1, pp 53-69

First online:

The end adjusts the means: Heterochromatin remodelling during terminal cell differentiation

  • Sergei A. GrigoryevAffiliated withDepartment of Biochemistry and Molecular Biology, H171, Penn State University College of Medicine, Milton S Hershey Medical Center Email author 
  • , Yaroslava A. BulynkoAffiliated withDepartment of Biochemistry and Molecular Biology, H171, Penn State University College of Medicine, Milton S Hershey Medical Center
  • , Evgenya Y. PopovaAffiliated withDepartment of Biochemistry and Molecular Biology, H171, Penn State University College of Medicine, Milton S Hershey Medical Center

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Abstract

All cells that constitute mature tissues in an eukaryotic organism undergo a multistep process of cell differentiation. At the terminal stage of this process, cells either cease to proliferate forever or rest for a very long period of time. During terminal differentiation, most of the genes that are required for cell ‘housekeeping’ functions, such as proto-oncogenes and other cell-cycle and cell proliferation genes, become stably repressed. At the same time, nuclear chromatin undergoes dramatic morphological and structural changes at the higher-order levels of chromatin organization. These changes involve both constitutively inactive chromosomal regions (constitutive heterochromatin) and the formerly active genes that become silenced and structurally modified to form facultative heterochromatin. Here we approach terminal cell differentiation as a unique system that allows us to combine biochemical, ultrastructural and molecular genetic techniques to study the relationship between the hierarchy of chromatin higher-order structures in the nucleus and its function(s) in dynamic packing of genetic material in a form that remains amenable to regulation of gene activity and other DNA-dependent cellular processes.

Key words

cell differentiation chromatin higher-order structure heterochromatin histone nucleosome