Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

AbstractATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

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Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

eLife ◽

10.7554/elife.35720 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 38

Author(s):

Ramasubramanian Sundaramoorthy ◽

Amanda L Hughes ◽

Hassane El-Mkami ◽

David G Norman ◽

Helder Ferreira ◽

...

Keyword(s):

Histone H3 ◽

Bound State ◽

Chromatin Remodelling ◽

Dna Interactions ◽

Histone Octamer ◽

Nucleosome Structure ◽

Protein Dna Interactions ◽

Dna Strands ◽

Regulate Protein ◽

Related Proteins

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein–DNA interactions. Here, we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

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Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor

Biochemical Journal ◽

10.1042/bj20021085 ◽

2002 ◽

Vol 367 (3) ◽

pp. 907-911 ◽

Cited By ~ 109

Author(s):

Sha TIAN ◽

Hetti POUKKA ◽

Jorma J. PALVIMO ◽

Olli A. JÄNNE

Keyword(s):

Glucocorticoid Receptor ◽

Transcriptional Activity ◽

Receptor Function ◽

Dna Interactions ◽

Mouse Mammary Tumour Virus ◽

Cellular Targets ◽

Attachment Sites ◽

Protein Dna Interactions ◽

Regulate Protein ◽

Virus Promoter

Small ubiquitin-related modifier-1 (SUMO-1) is covalently attached to many cellular targets to regulate protein—protein and protein—DNA interactions, as well as localization and stability of the target protein. The SUMO-1-conjugating E2 enzyme Ubc9 is known to interact with the glucocorticoid receptor (GR), a ligand-dependent transcription factor. In the present study, we show that GR is post-translationally modified by SUMO-1 (sumoylated) in a ligand-enhanced fashion. We identify experimentally three consensus SUMO attachment sites, two in the N-terminal transactivation region and one in the ligand-binding domain of GR. The two N-terminal sites are the major acceptor sites for SUMO-1 attachment. Mutation of these sites enhances transcriptional activity of GR on minimal promoters, but has no clear effect on the more complex mouse mammary tumour virus promoter. Thus SUMO-1 modification of GR influences receptor function in a promoter context-dependent fashion.

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