Identification of two independent nucleosome-binding domains in the transcriptional co-activator SPBP.

Abstract

Transcriptional regulation requires co-ordinated action of transcription factors, co-activator complexes and general transcription factors to access specific loci in the dense chromatin structure. In the present study we demonstrate that the transcriptional co-regulator SPBP [stromelysin-1 PDGF (platelet-derived growth factor)-responsive element binding protein] contains two independent chromatin-binding domains, the SPBP-(1551-1666) region and the C-terminal extended PHD [ePHD/ADD (extended plant homeodomain/ATRX-DNMT3-DNMT3L)] domain. The region 1551-1666 is a novel core nucleosome-interaction domain located adjacent to the AT-hook motif in the DNA-binding domain. This novel nucleosome-binding region is critically important for proper localization of SPBP in the cell nucleus. The ePHD/ADD domain associates with nucleosomes in a histone tail-dependent manner, and has significant impact on the dynamic interaction between SPBP and chromatin. Furthermore, SPBP and its homologue RAI1 (retinoic-acid-inducible protein 1), are strongly enriched on chromatin in interphase HeLa cells, and both proteins display low nuclear mobility. RAI1 contains a region with homology to the novel nucleosome-binding region SPBP-(1551-1666) and an ePHD/ADD domain with ability to bind nucleosomes. These results indicate that the transcriptional co-regulator SPBP and its homologue RAI1 implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome both belong to the expanding family of chromatin-binding proteins containing several domains involved in specific chromatin interactions.

• Authors: Sagar Darvekar, Sylvia Sagen Johnsen, Agnete Bratsberg Eriksen, Terje Johansen, Eva Sjøttem
• Journal: The Biochemical journal (Biochem J) Vol. 442 Issue 1 Pg. 65-75 (Feb 15 2012) ISSN: 1470-8728 [Electronic] England
• PMID: 22081970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• Euchromatin
• Nucleosomes
• RAI1 protein, human
• TCF20 protein, human
• Trans-Activators
• Transcription Factors

Topics

• Chromatin (metabolism)
• Euchromatin (metabolism)
• HeLa Cells
• Humans
• Nucleosomes (metabolism)
• Protein Structure, Tertiary (physiology)
• Smith-Magenis Syndrome
• Trans-Activators
• Transcription Factors (chemistry, metabolism)