DNA looping and Sp1 multimer links: A mechanism for transcriptional synergism and enhancement

Journal Article · Mon Jul 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.13.5670· OSTI ID:6101169

Mastrangelo, I A; Wall, J S; Hough, P V.C. ^[1]; Courey, A J ^[2]; Jackson, S P ^[3]

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1. Brookhaven National Lab., Upton, NY (United States)
2. Univ. of California, Los Angeles (United States)
3. Univ. of California, Berkeley (United States)

Using conventional and scanning transmission electron microscopy, the authors have examined the physical basis of long-range enhancer effects between distal and proximal elements in a eukaryotic promoter. Specifically, they studied binding of human transcription factor Sp1 to 10-base-pair G + C-rich elements (GC boxes) located at {minus}100 and +1700 relative to the RNA start site. It was previously observed that the distantly located site functions in synergism with the promoter-proximal site to strongly activate transcription in vivo. Here they demonstrate that this synergism is likely to be a direct consequence of interactions between remote and local Sp1, the remote Sp1 translocated to the promoter by a DNA loop. Scanning transmission electron microscopy shows that Sp1 initially forms a tetramer and subsequently assembles multiple tetramers stacked in register at the DNA loop juncture. This unexpected finding not only provides the physical basis for loop formation but also defines a biological process leading to strongly increased concentration of activator protein at the promoter. The mechanism may unify the problem of transcriptional activation by removing enhancer action as a separate class of regulatory activity.

• OSTI ID: 6101169
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:13; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA
TRANSMISSION ELECTRON MICROSCOPY
TRANSCRIPTION
GENE REGULATION
TRANSCRIPTION FACTORS
STRUCTURAL MODELS
GENE REPRESSORS
SCANNING ELECTRON MICROSCOPY
SYNERGISM
ELECTRON MICROSCOPY
MICROSCOPY
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PROTEINS
550200* - Biochemistry