The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation.
Histone variants are nonallelic isoforms of canonical histones, and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of theDrosophilaDAXX-like protein (DLP) by using both fly genetic approaches and protein biochemistry. DLP specifically interacts with H3.3 and shows a prominent localization on the base of the X chromosome, where it appears to act in concert with XNP, theDrosophilahomolog of ATRX, in heterochromatin assembly and maintenance. The functional association between DLP and XNP is further supported by a series of experiments that illustrate genetic interactions and the DLP-XNP-dependent localization of specific chromosomal proteins. In addition, DLP both participates in the RI deposition of H3.3 and associates with anti-silencing factor 1 (ASF1). We suggest, in agreement with a recently proposed model, that DLP and ASF1 are part of a predeposition complex, which is recruited by XNP and is necessary to prevent DNA exposure in the nucleus.
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire, UdS, CNRS, INSERM, Equipe Labélisée Ligue contre le Cancer, Illkirch, France.
Catherine
C
Fromental-Ramain
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire, UdS, CNRS, INSERM, Equipe Labélisée Ligue contre le Cancer, Illkirch, France phr@igbmc.fr hamiche@igbmc.fr.
Philippe
P
Ramain
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire, UdS, CNRS, INSERM, Equipe Labélisée Ligue contre le Cancer, Illkirch, France phr@igbmc.fr hamiche@igbmc.fr.
Ali
A
Hamiche
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004261:DNA Replication; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004843:Epistasis, Genetic; D022041:Euchromatin / Q000378:metabolism; D005260:Female; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C526347:Daxx protein, Drosophila; D029721:Drosophila Proteins; D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; C491642:asf1 protein, Drosophila; C541123:XNP protein, Drosophila; D004265:DNA Helicases
ASF1; DLP; H3.3; XNP; heterochromatin; histone variant