title: Gene target specificity of the Super Elongation Complex (SEC) family: how HIV-1 Tat employs selected SEC members to activate viral transcription.
abstract: The AF4/FMR2 proteins AFF1 and AFF4 act as a scaffold to assemble the Super Elongation Complex (SEC) that strongly activates transcriptional elongation of HIV-1 and cellular genes. Although they can dimerize, it is unclear whether the dimers exist and function within a SEC in vivo. Furthermore, it is unknown whether AFF1 and AFF4 function similarly in mediating SEC-dependent activation of diverse genes. Providing answers to these questions, our current study shows that AFF1 and AFF4 reside in separate SECs that display largely distinct gene target specificities. While the AFF1-SEC is more potent in supporting HIV-1 transactivation by the viral Tat protein, the AFF4-SEC is more important for HSP70 induction upon heat shock. The functional difference between AFF1 and AFF4 in Tat-transactivation has been traced to a single amino acid variation between the two proteins, which causes them to enhance the affinity of Tat for P-TEFb, a key SEC component, with different efficiency. Finally, genome-wide analysis confirms that the genes regulated by AFF1-SEC and AFF4-SEC are largely non-overlapping and perform distinct functions. Thus, the SEC represents a family of related complexes that exist to increase the regulatory diversity and gene control options during transactivation of diverse cellular and viral genes.
authors.affiliation: Innovation Center of Cell Signaling Network, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, Fujian, China Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Huasong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Zichong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schulze-Gahmen
authors.affiliation: Innovation Center of Cell Signaling Network, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, Fujian, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA qzhou@berkeley.edu.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C471348:AFF4 protein, human; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D017411:Ribonucleoproteins, Small Nuclear; D035602:Transcriptional Elongation Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C081449:AFF1 protein, human; D042925:Positive Transcriptional Elongation Factor B