Multivalency regulates activity in an intrinsically disordered
transcription factor

J 2018

Multivalency regulates activity in an intrinsically disordered transcription factor

CLARK, S., J.B. MYERS, A. KING, Radovan FIALA, Jiří NOVÁČEK et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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.

Links

653706, interní kód MU

Name: 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)

Citovat

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.

@article{1507897,
   author = {Clark, S. and Myers, J.B. and King, A. and Fiala, Radovan and Nováček, Jiří and Pearce, G. and Heierhorst, J. and Reichow, S.L. and Barbar, E.J.},
   article_location = {CAMBRIDGE},
   article_number = {MAY},
   doi = {http://dx.doi.org/10.7554/eLife.36258},
   keywords = {DYNEIN LIGHT-CHAIN; BINDING PROTEIN CBP; C-TERMINAL DOMAIN; MULTISITE PHOSPHORYLATION; UNSTRUCTURED REGION; DNA-BINDING; LC8; COMPLEX; DYNLL1; ASCIZ},
   language = {eng},
   issn = {2050-084X},
   journal = {elife},
   title = {Multivalency regulates activity in an intrinsically disordered transcription factor},
   volume = {7},
   year = {2018}
}

TY  - JOUR
ID  - 1507897
AU  - Clark, S. - Myers, J.B. - King, A. - Fiala, Radovan - Nováček, Jiří - Pearce, G. - Heierhorst, J. - Reichow, S.L. - Barbar, E.J.
PY  - 2018
TI  - Multivalency regulates activity in an intrinsically disordered transcription factor
JF  - elife
VL  - 7
IS  - MAY
SP  - 1-28
EP  - 1-28
PB  - ELIFE SCIENCES PUBLICATIONS LTD
SN  - 2050084X
KW  - DYNEIN LIGHT-CHAIN
KW  - BINDING PROTEIN CBP
KW  - C-TERMINAL DOMAIN
KW  - MULTISITE PHOSPHORYLATION
KW  - UNSTRUCTURED REGION
KW  - DNA-BINDING
KW  - LC8
KW  - COMPLEX
KW  - DYNLL1
KW  - ASCIZ
N2  - 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.
ER  -

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. \textit{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.

Detailed Information on Publication Record