The MYST domain acetyltransferase Chameau functions in epigenetic mechanisms of transcriptional repression.
Reversible acetylation of histone tails plays an important role in chromatin remodelling and regulation of gene activity. While modification by histone acetyltransferase (HAT) is usually linked to transcriptional activation, we provide here evidence for HAT function in several types of epigenetic repression. Chameau (Chm), a new Drosophila member of the MYST HAT family, dominantly suppresses position effect variegation (PEV), is required for the maintenance of Hox gene silencing by Polycomb group (PcG) proteins, and can partially substitute for the MYST Sas2 HAT in yeast telomeric position effect (TPE). Finally, we provide in vivo evidence that the acetyltransferase activity of Chm is required in these processes, since a variant protein mutated in the catalytic domain no longer rescues PEV modification, telomeric silencing of SAS2-deficient yeast cells, nor lethality of chm mutant flies. These findings emphasize the role of an acetyltransferase in gene silencing, which supports, according to the histone code hypothesis, that transcription at a particular locus is determined by a precise combination of histone tail modifications rather than by overall acetylation levels.
Grienenberger
Aurélie
A
Laboratoire de Génétique et Physiologie du Développement, Institut de Biologie du Développement de Marseille, CNRS/INSERM/Université de la Méditerranée, Parc Scientifique de Luminy, Case 907, 13288 Marseille Cedex 9, France.
Miotto
Benoit
B
Sagnier
Thierry
T
Cavalli
Giacomo
G
Schramke
Vera
V
Geli
Vincent
V
Mariol
Marie Christine
MC
Berenger
Hélene
H
Graba
Yacine
Y
Pradel
Jacques
J
D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006570:Heterochromatin / Q000502:physiology; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D008297:Male; D009154:Mutation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000502:physiology
D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C467710:chm protein, Drosophila; D051548:Histone Acetyltransferases