Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Multivalency regulates activity in an intrinsically disordered transcription factor

S. Clark, JB. Myers, A. King, R. Fiala, J. Novacek, G. Pearce, J. Heierhorst, SL. Reichow, EJ. Barbar,

. 2018 ; 7 (-) : . [pub] 20180501

Language English Country England, Great Britain

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19035274

Grant support
R35GM124779 NIGMS NIH HHS - United States
S10 OD018518 NIH HHS - United States
R35 GM124779 NIGMS NIH HHS - United States
R01-084276 NIGMS NIH HHS - United States
R01 GM084276 NIGMS NIH HHS - United States
1S10OD018518 NIH HHS - United States

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19035274
003      
CZ-PrNML
005      
20191011093825.0
007      
ta
008      
191007s2018 enk f 000 0|eng||
009      
AR
024    7_
$a 10.7554/eLife.36258 $2 doi
035    __
$a (PubMed)29714690
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Clark, Sarah $u Department of Biochemistry and Biophysics, Oregon State University, Oregon, United States.
245    10
$a Multivalency regulates activity in an intrinsically disordered transcription factor / $c S. Clark, JB. Myers, A. King, R. Fiala, J. Novacek, G. Pearce, J. Heierhorst, SL. Reichow, EJ. Barbar,
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a cytoplazmatické dyneiny $x chemie $x genetika $x metabolismus $7 D056445
650    _2
$a proteiny Drosophily $x chemie $x genetika $x metabolismus $7 D029721
650    _2
$a Drosophila melanogaster $x růst a vývoj $x metabolismus $x fyziologie $7 D004331
650    _2
$a dyneiny $x chemie $x genetika $x metabolismus $7 D004398
650    12
$a regulace genové exprese $7 D005786
650    _2
$a lidé $7 D006801
650    _2
$a vnitřně neuspořádané proteiny $x genetika $x metabolismus $7 D064267
650    _2
$a transkripční faktory $x chemie $x genetika $x metabolismus $7 D014157
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Myers, Janette B $u Department of Chemistry, Portland State University, Oregon, United States.
700    1_
$a King, Ashleigh $u St. Vincent's Institute of Medical Research, The University of Melbourne, Victoria, Australia. Department of Medicine, St. Vincent's Health, The University of Melbourne, Victoria, Australia.
700    1_
$a Fiala, Radovan $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
700    1_
$a Novacek, Jiri $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
700    1_
$a Pearce, Grant $u School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
700    1_
$a Heierhorst, Jörg $u St. Vincent's Institute of Medical Research, The University of Melbourne, Victoria, Australia. Department of Medicine, St. Vincent's Health, The University of Melbourne, Victoria, Australia.
700    1_
$a Reichow, Steve L $u Department of Chemistry, Portland State University, Oregon, United States.
700    1_
$a Barbar, Elisar J $u Department of Biochemistry and Biophysics, Oregon State University, Oregon, United States.
773    0_
$w MED00188753 $t eLife $x 2050-084X $g Roč. 7, č. - (2018)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29714690 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20191007 $b ABA008
991    __
$a 20191011094245 $b ABA008
999    __
$a ok $b bmc $g 1451934 $s 1073824
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 7 $c - $e 20180501 $i 2050-084X $m eLife $n eLife $x MED00188753
GRA    __
$a R35GM124779 $p NIGMS NIH HHS $2 United States
GRA    __
$a S10 OD018518 $p NIH HHS $2 United States
GRA    __
$a R35 GM124779 $p NIGMS NIH HHS $2 United States
GRA    __
$a R01-084276 $p NIGMS NIH HHS $2 United States
GRA    __
$a R01 GM084276 $p NIGMS NIH HHS $2 United States
GRA    __
$a 1S10OD018518 $p NIH HHS $2 United States
LZP    __
$a Pubmed-20191007
Back

Find record

Citation metrics

Archiving options