Distance and helical phase dependence of synergistic transcription activation in cis-regulatory module.
Deciphering of the spatial and stereospecific constraints on synergistic transcription activation mediated between activators bound to cis-regulatory elements is important for understanding gene regulation and remains largely unknown. It has been commonly believed that two activators will activate transcription most effectively when they are bound on the same face of DNA double helix and within a boundary distance from the transcription initiation complex attached to the TATA box. In this work, we studied the spatial and stereospecific constraints on activation by multiple copies of bound model activators using a series of engineered relative distances and stereospecific orientations. We observed that multiple copies of the activators GAL4-VP16 and ZEBRA bound to engineered promoters activated transcription more effectively when bound on opposite faces of the DNA double helix. This phenomenon was not affected by the spatial relationship between the proximal activator and initiation complex. To explain these results, we proposed the novel concentration field model, which posits the effective concentration of bound activators, and therefore the transcription activation potential, is affected by their stereospecific positioning. These results could be used to understand synergistic transcription activation anew and to aid the development of predictive models for the identification of cis-regulatory elements.
The State Key Laboratory of Pharmaceutical Biotechnology and Affiliated Stomatological Hospital, Nanjing University, Nanjing, People's Republic of China.
Qilai
Q
Huang
Chenguang
C
Gong
Jiahuang
J
Li
Zhu
Z
Zhuo
Yuan
Y
Chen
Jin
J
Wang
Zi-Chun
ZC
Hua
D001483:Base Sequence / Q000502:physiology*; D001665:Binding Sites; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection
C063676:BZLF1 protein, Herpesvirus 4, Human; D017405:Herpes Simplex Virus Protein Vmw65; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators