UHRF1 recruits the histone acetyltransferase Tip60 and controls its expression and activity.
Tat-interactive protein, 60kDa (Tip60) is a histone acetyltransferase with specificity toward lysine 5 of histone H2A (H2AK5) and plays multiple roles in chromatin remodeling processes. Co-immunoprecipitation experiments performed on Jurkat cells, showed that Tip60 is present in the same macro-molecular complex as UHRF1 (Ubiquitin-like containing PHD and RING domain 1), DNMT1 (DNA methyltransferase 1), and HDAC1 (histone deacetylase 1). Furthermore, immunocytochemistry experiments confirmed that Tip60 co-localizes with the UHRF1/DNMT1 complex. Although down-regulation of UHRF1 by RNA interference enhanced Tip60 expression, a significant decrease of the level of acetylated H2AK5 was observed. Consistently, we have observed that down-regulation of Tip60 and DNMT1 by RNA interference, dramatically reduced the levels of acetylated H2AK5. Altogether, these results suggest that Tip60 is a novel partner of the epigenetic integration platform interplayed by UHRF1, DNMT1 and HDAC1 involved in the epigenetic code replication.
Achour
Mayada
M
CNRS UMR 7213, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France.
Fuhrmann
Guy
G
Alhosin
Mahmoud
M
Rondé
Philippe
P
Chataigneau
Thierry
T
Mousli
Marc
M
Schini-Kerth
Valérie B
VB
Bronner
Christian
C
D000107:Acetylation; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008239:Lysine / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D044767:Ubiquitin-Protein Ligases
D022762:CCAAT-Enhancer-Binding Proteins; D006657:Histones; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D008239:Lysine