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@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 a E.J. BARBAR. Multivalency regulates activity in an intrinsically disordered transcription factor. \textit{elife}. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD, roč.~7, MAY, s.~1-28. ISSN~2050-084X. doi:10.7554/eLife.36258. 2018.
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