Gene activation and gene silencing: a subtle equilibrium.
The genetic make-up of a cell resides entirely in its DNA. Now that the nucleotide sequence of several genomes has been determined, the major challenging problem is to understand how cell differentiation, proliferation or death are controlled. Major steps include analysis of the determinants of the cell cycle, the unravelling of RNAs and proteins involved in the control of gene expression and the dissection of the protein-destruction machinery. The successive steps to be considered are transcription of RNA on the DNA template, mRNA stabilization or degradation, and mRNA translation and protein localization in the right cell compartment. Gene expression or gene silencing is the result of many DNA-RNA-protein interactions and chromatin is among the key regulators of gene expression. Open chromatin (euchromatin) allows expression of the DNA message. This chromatin structure is generally characterized by the presence on the gene promoters of transcription complexes associated with histone acetyltransferases (HATs). On the contrary, closed chromatin (heterochromatin) is poorly acetylated and more condensed. It contains histone deacetylases (HDACs), potentially associated with DNA methyltransferases (DNMTs). DNMT activity leads to methylation and silencing of the DNA. Thus, a major problem in the field of gene regulation resides in understanding chromatin structure at each promoter, a formidable task for the years to come.
Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Service de Chimie Biologique, Laboratoire de Virologie Moléculaire, Rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.
Vincent
V
Quivy
Claire
C
Calomme
Ann
A
Dekoninck
Dominique
D
Demonte
Françoise
F
Bex
Isabelle
I
Lamsoul
Caroline
C
Vanhulle
Arsène
A
Burny
Carine
C
Van Lint
D000107:Acetylation; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D012190:Retroviridae / Q000235:genetics; D015533:Transcriptional Activation
D006570:Heterochromatin; D006657:Histones