1yui

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SOLUTION NMR STRUCTURE OF THE GAGA FACTOR/DNA COMPLEX, REGULARIZED MEAN STRUCTURESOLUTION NMR STRUCTURE OF THE GAGA FACTOR/DNA COMPLEX, REGULARIZED MEAN STRUCTURE

Structural highlights

1yui is a 3 chain structure with sequence from Drosophila melanogaster. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GAGA_DROME Transcriptional activator that functions by regulating chromatin structure. Overcomes the repressive effects of chromatin by promoting the open chromatin conformation in promoter gene regions, thereby allowing access to other transcription factors. Binds to DNA Polycomb response elements (PREs) at the bithorax complex and to the proximal region of the engrailed promoter, and positively regulates transcription of many genes including homeotic ones. Binds to the DNA sequence (GA)n, with optimal binding to the pentamer 5'-GAGAG-3'. Binds DNA as an oligomer. May also act as a transcriptional repressor, maintaining the repressed state of genes including lolal, and down-regulating its own transcription. Required for dosage compensation in males and may be involved in oogenesis. Also has a role in nuclear division.[1] [2] [3] [4] [5] [6] [7] [8]

Publication Abstract from PubMed

The structure of a complex between the DNA binding domain of the GAGA factor (GAGA-DBD) and an oligonucleotide containing its GAGAG consensus binding site has been determined by nuclear magnetic resonance spectroscopy. The GAGA-DBD comprises a single classical Cys2-His2 zinc finger core, and an N-terminal extension containing two highly basic regions, BR1 and BR2. The zinc finger core binds in the major groove and recognizes the first three GAG bases of the consensus in a manner similar to that seen in other classical zinc finger-DNA complexes. Unlike the latter, which require tandem zinc finger repeats with a minimum of two units for high affinity binding, the GAGA-DBD makes use of only a single finger complemented by BR1 and BR2. BR2 forms a helix that interacts in the major groove recognizing the last G of the consensus, while BR1 wraps around the DNA in the minor groove and recognizes the A in the fourth position of the consensus. The implications of the structure of the GAGA-DBD-DNA complex for chromatin remodelling are discussed.

The solution structure of a specific GAGA factor-DNA complex reveals a modular binding mode.,Omichinski JG, Pedone PV, Felsenfeld G, Gronenborn AM, Clore GM Nat Struct Biol. 1997 Feb;4(2):122-32. PMID:9033593[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Soeller WC, Oh CE, Kornberg TB. Isolation of cDNAs encoding the Drosophila GAGA transcription factor. Mol Cell Biol. 1993 Dec;13(12):7961-70. PMID:7504178
  2. Benyajati C, Mueller L, Xu N, Pappano M, Gao J, Mosammaparast M, Conklin D, Granok H, Craig C, Elgin S. Multiple isoforms of GAGA factor, a critical component of chromatin structure. Nucleic Acids Res. 1997 Aug 15;25(16):3345-53. PMID:9241251
  3. Bhat KM, Farkas G, Karch F, Gyurkovics H, Gausz J, Schedl P. The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division. Development. 1996 Apr;122(4):1113-24. PMID:8620838
  4. Kosoy A, Pagans S, Espinas ML, Azorin F, Bernues J. GAGA factor down-regulates its own promoter. J Biol Chem. 2002 Nov 1;277(44):42280-8. Epub 2002 Aug 27. PMID:12200449 doi:http://dx.doi.org/10.1074/jbc.M207505200
  5. Shimojima T, Okada M, Nakayama T, Ueda H, Okawa K, Iwamatsu A, Handa H, Hirose S. Drosophila FACT contributes to Hox gene expression through physical and functional interactions with GAGA factor. Genes Dev. 2003 Jul 1;17(13):1605-16. Epub 2003 Jun 18. PMID:12815073 doi:http://dx.doi.org/10.1101/gad.1086803
  6. Mishra K, Chopra VS, Srinivasan A, Mishra RK. Trl-GAGA directly interacts with lola like and both are part of the repressive complex of Polycomb group of genes. Mech Dev. 2003 Jun;120(6):681-9. PMID:12834867
  7. Bejarano F, Busturia A. Function of the Trithorax-like gene during Drosophila development. Dev Biol. 2004 Apr 15;268(2):327-41. PMID:15063171 doi:http://dx.doi.org/10.1016/j.ydbio.2004.01.006
  8. Greenberg AJ, Yanowitz JL, Schedl P. The Drosophila GAGA factor is required for dosage compensation in males and for the formation of the male-specific-lethal complex chromatin entry site at 12DE. Genetics. 2004 Jan;166(1):279-89. PMID:15020425
  9. Omichinski JG, Pedone PV, Felsenfeld G, Gronenborn AM, Clore GM. The solution structure of a specific GAGA factor-DNA complex reveals a modular binding mode. Nat Struct Biol. 1997 Feb;4(2):122-32. PMID:9033593
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