CLARK, S., J.B. MYERS, A. KING, Radovan FIALA, Jiří NOVÁČEK, G. PEARCE, J. HEIERHORST, S.L. REICHOW and E.J. BARBAR. Multivalency regulates activity in an intrinsically disordered transcription factor. elife. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD, 2018, vol. 7, MAY, p. 1-28. ISSN 2050-084X. Available from: https://dx.doi.org/10.7554/eLife.36258.
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Basic information
Original name Multivalency regulates activity in an intrinsically disordered transcription factor
Authors CLARK, S. (840 United States of America), J.B. MYERS (840 United States of America), A. KING (36 Australia), Radovan FIALA (203 Czech Republic, belonging to the institution), Jiří NOVÁČEK (203 Czech Republic, guarantor, belonging to the institution), G. PEARCE (554 New Zealand), J. HEIERHORST (36 Australia), S.L. REICHOW (840 United States of America) and E.J. BARBAR (840 United States of America).
Edition elife, CAMBRIDGE, ELIFE SCIENCES PUBLICATIONS LTD, 2018, 2050-084X.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 7.551
RIV identification code RIV/00216224:14740/18:00106665
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.7554/eLife.36258
UT WoS 000432725100001
Keywords in English DYNEIN LIGHT-CHAIN; BINDING PROTEIN CBP; C-TERMINAL DOMAIN; MULTISITE PHOSPHORYLATION; UNSTRUCTURED REGION; DNA-BINDING; LC8; COMPLEX; DYNLL1; ASCIZ
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 19/3/2019 16:32.
Abstract
The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product of its main target gene, the hub protein LC8 (DYNLL1). Using a combination of biophysical methods, structural analysis by NMR and electron microscopy, and cellular transcription assays, we developed a model that proposes a concerted role of intrinsic disorder and multiple LC8 binding events in regulating LC8 transcription. We demonstrate that the long intrinsically disordered C -terminal domain of ASCIZ binds LC8 to form a dynamic ensemble of complexes with a gradient of transcriptional activity that is inversely proportional to LC8 occupancy. The preference for low occupancy complexes at saturating LC8 concentrations with both human and Drosophila ASCIZ indicates that negative cooperativity is an important feature of ASCIZ-LC8 interactions. The prevalence of intrinsic disorder and multivalency among transcription factors suggests that formation of heterogeneous, dynamic complexes is a widespread mechanism for tuning transcriptional regulation.
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653706, interní kód MUName: iNEXT - Infrastructure for NMR, EM and X-ray crystallography for translational research (Acronym: iNEXT)
Investor: European Union, iNEXT - Infrastructure for NMR, EM and X-ray crystallography for translational research, RI Research Infrastructures (Excellent Science)
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