| Structural highlights
Function
[SMBT_DROME] Polycomb group (PcG) protein that binds to the Polycomb response elements (PREs) found in the regulatory regions of many genes. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via the methylation of histones, rendering chromatin heritably changed in its expressibility. Necessary but not sufficient to recruit a functional PcG repressive complex that represses target genes, suggesting that the recruitment of the distinct PRC1 complex is also required to allow a subsequent repression.[1] [PHO_DROME] Polycomb group (PcG) protein that binds to the 5'-CNGCCATNNNNG-3' sequence found in the regulatory regions of many genes. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via the methylation of histones, rendering chromatin heritably changed in its expressibility. Probably targets the Esc/E(z) complex to DNA. Necessary but not sufficient to recruit a functional PcG repressive complex that represses target genes, suggesting that the recruitment of the distinct PRC1 complex is also required to allow a subsequent repression.[2] [3] Proposed core component of the chromatin remodeling Ino80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair (By similarity).[4] [5]
Publication Abstract from PubMed
Polycomb group (PcG) protein complexes repress developmental regulator genes by modifying their chromatin. How different PcG proteins assemble into complexes and are recruited to their target genes is poorly understood. Here, we report the crystal structure of the core of the Drosophila PcG protein complex Pleiohomeotic (Pho)-repressive complex (PhoRC), which contains the Polycomb response element (PRE)-binding protein Pho and Sfmbt. The spacer region of Pho, separated from the DNA-binding domain by a long flexible linker, forms a tight complex with the four malignant brain tumor (4MBT) domain of Sfmbt. The highly conserved spacer region of the human Pho ortholog YY1 binds three of the four human 4MBT domain proteins in an analogous manner but with lower affinity. Comparison of the Drosophila Pho:Sfmbt and human YY1:MBTD1 complex structures provides a molecular explanation for the lower affinity of YY1 for human 4MBT domain proteins. Structure-guided mutations that disrupt the interaction between Pho and Sfmbt abolish formation of a ternary Sfmbt:Pho:DNA complex in vitro and repression of developmental regulator genes in Drosophila. PRE tethering of Sfmbt by Pho is therefore essential for Polycomb repression in Drosophila. Our results support a model where DNA tethering of Sfmbt by Pho and multivalent interactions of Sfmbt with histone modifications and other PcG proteins create a hub for PcG protein complex assembly at PREs.
Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.,Alfieri C, Gambetta MC, Matos R, Glatt S, Sehr P, Fraterman S, Wilm M, Muller J, Muller CW Genes Dev. 2013 Nov 1;27(21):2367-79. doi: 10.1101/gad.226621.113. PMID:24186981[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Klymenko T, Papp B, Fischle W, Kocher T, Schelder M, Fritsch C, Wild B, Wilm M, Muller J. A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities. Genes Dev. 2006 May 1;20(9):1110-22. Epub 2006 Apr 17. PMID:16618800 doi:http://dx.doi.org/10.1101/gad.377406
- ↑ Brown JL, Mucci D, Whiteley M, Dirksen ML, Kassis JA. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Mol Cell. 1998 Jun;1(7):1057-64. PMID:9651589
- ↑ Fritsch C, Brown JL, Kassis JA, Muller J. The DNA-binding polycomb group protein pleiohomeotic mediates silencing of a Drosophila homeotic gene. Development. 1999 Sep;126(17):3905-13. PMID:10433918
- ↑ Brown JL, Mucci D, Whiteley M, Dirksen ML, Kassis JA. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Mol Cell. 1998 Jun;1(7):1057-64. PMID:9651589
- ↑ Fritsch C, Brown JL, Kassis JA, Muller J. The DNA-binding polycomb group protein pleiohomeotic mediates silencing of a Drosophila homeotic gene. Development. 1999 Sep;126(17):3905-13. PMID:10433918
- ↑ Alfieri C, Gambetta MC, Matos R, Glatt S, Sehr P, Fraterman S, Wilm M, Muller J, Muller CW. Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements. Genes Dev. 2013 Nov 1;27(21):2367-79. doi: 10.1101/gad.226621.113. PMID:24186981 doi:http://dx.doi.org/10.1101/gad.226621.113
|
