Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter.
Activation of the human immunodeficiency virus type-1 (HIV-1) promoter in infected cells requires the sequential recruitment of several cellular factors to facilitate the formation of a processive elongation complex. The nucleosomal reorganization of the HIV-1 long terminal repeat (LTR) observed upon Tat stimulation suggests that chromatin-remodeling complexes could play a role during this process. Here, we reported that Tat interacts directly with Brm, a DNA-dependent ATPase subunit of the SWI/SNF chromatin-remodeling complex, to activate the HIV-1 LTR. Inhibition of Brm via small interfering RNAs impaired Tat-mediated transactivation of an integrated HIV-1 promoter. Furthermore, Brm is recruited in vivo to the HIV-1 LTR in a Tat-dependent manner. Interestingly, we found that Tat/Brm interaction is regulated by Tat lysine 50 acetylation. These data show the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling complex to HIV-1 promoter in the activation of the LTR.
Tréand
Céline
C
Institut Cochin, Département de Génétique et Développement, Paris, France.
du Chéné
Isaure
I
Brès
Vanessa
V
Kiernan
Rosemary
R
Benarous
Richard
R
Benkirane
Monsef
M
Emiliani
Stéphane
S
D000107:Acetylation; D020816:Amino Acid Motifs; D001120:Arginine / Q000235:genetics; D002460:Cell Line; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D021122:Protein Subunits; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D001120:Arginine; D008239:Lysine