Deciphering the Sox-Oct partner code by quantitative cooperativity measurements

Calista K L Ng, Noel X. Li, Sheena Chee, Shyam Prabhakar, Prasanna Kolatkar, Ralf Jauch

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Several Sox-Oct transcription factor (TF) combinations have been shown to cooperate on diverse enhancers to determine cell fates. Here, we developed a method to quantify biochemically the Sox-Oct cooperation and assessed the pairing of the high-mobility group (HMG) domains of 11 Sox TFs with Oct4 on a series of composite DNA elements. This way, we clustered Sox proteins according to their dimerization preferences illustrating that Sox HMG domains evolved different propensities to cooperate with Oct4. Sox2, Sox14, Sox21 and Sox15 strongly cooperate on the canonical element but compete with Oct4 on a recently discovered compressed element. Sry also cooperates on the canonical element but binds additively to the compressed element. In contrast, Sox17 and Sox4 cooperate more strongly on the compressed than on the canonical element. Sox5 and Sox18 show some cooperation on both elements, whereas Sox8 and Sox9 compete on both elements. Testing rationally mutated Sox proteins combined with structural modeling highlights critical amino acids for differential Sox-Oct4 partnerships and demonstrates that the cooperativity correlates with the efficiency in producing induced pluripotent stem cells. Our results suggest selective Sox-Oct partnerships in genome regulation and provide a toolset to study protein cooperation on DNA.

Original languageEnglish
Pages (from-to)4933-4941
Number of pages9
JournalNucleic Acids Research
Volume40
Issue number11
DOIs
Publication statusPublished - 1 Jun 2012
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Proteins
DNA
Dimerization
Transcription Factors
Genome
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Deciphering the Sox-Oct partner code by quantitative cooperativity measurements. / Ng, Calista K L; Li, Noel X.; Chee, Sheena; Prabhakar, Shyam; Kolatkar, Prasanna; Jauch, Ralf.

In: Nucleic Acids Research, Vol. 40, No. 11, 01.06.2012, p. 4933-4941.

Research output: Contribution to journalArticle

Ng, Calista K L ; Li, Noel X. ; Chee, Sheena ; Prabhakar, Shyam ; Kolatkar, Prasanna ; Jauch, Ralf. / Deciphering the Sox-Oct partner code by quantitative cooperativity measurements. In: Nucleic Acids Research. 2012 ; Vol. 40, No. 11. pp. 4933-4941.
@article{ce500d90ab8f41fda51ba252b023fb20,
title = "Deciphering the Sox-Oct partner code by quantitative cooperativity measurements",
abstract = "Several Sox-Oct transcription factor (TF) combinations have been shown to cooperate on diverse enhancers to determine cell fates. Here, we developed a method to quantify biochemically the Sox-Oct cooperation and assessed the pairing of the high-mobility group (HMG) domains of 11 Sox TFs with Oct4 on a series of composite DNA elements. This way, we clustered Sox proteins according to their dimerization preferences illustrating that Sox HMG domains evolved different propensities to cooperate with Oct4. Sox2, Sox14, Sox21 and Sox15 strongly cooperate on the canonical element but compete with Oct4 on a recently discovered compressed element. Sry also cooperates on the canonical element but binds additively to the compressed element. In contrast, Sox17 and Sox4 cooperate more strongly on the compressed than on the canonical element. Sox5 and Sox18 show some cooperation on both elements, whereas Sox8 and Sox9 compete on both elements. Testing rationally mutated Sox proteins combined with structural modeling highlights critical amino acids for differential Sox-Oct4 partnerships and demonstrates that the cooperativity correlates with the efficiency in producing induced pluripotent stem cells. Our results suggest selective Sox-Oct partnerships in genome regulation and provide a toolset to study protein cooperation on DNA.",
author = "Ng, {Calista K L} and Li, {Noel X.} and Sheena Chee and Shyam Prabhakar and Prasanna Kolatkar and Ralf Jauch",
year = "2012",
month = "6",
day = "1",
doi = "10.1093/nar/gks153",
language = "English",
volume = "40",
pages = "4933--4941",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Deciphering the Sox-Oct partner code by quantitative cooperativity measurements

AU - Ng, Calista K L

AU - Li, Noel X.

AU - Chee, Sheena

AU - Prabhakar, Shyam

AU - Kolatkar, Prasanna

AU - Jauch, Ralf

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Several Sox-Oct transcription factor (TF) combinations have been shown to cooperate on diverse enhancers to determine cell fates. Here, we developed a method to quantify biochemically the Sox-Oct cooperation and assessed the pairing of the high-mobility group (HMG) domains of 11 Sox TFs with Oct4 on a series of composite DNA elements. This way, we clustered Sox proteins according to their dimerization preferences illustrating that Sox HMG domains evolved different propensities to cooperate with Oct4. Sox2, Sox14, Sox21 and Sox15 strongly cooperate on the canonical element but compete with Oct4 on a recently discovered compressed element. Sry also cooperates on the canonical element but binds additively to the compressed element. In contrast, Sox17 and Sox4 cooperate more strongly on the compressed than on the canonical element. Sox5 and Sox18 show some cooperation on both elements, whereas Sox8 and Sox9 compete on both elements. Testing rationally mutated Sox proteins combined with structural modeling highlights critical amino acids for differential Sox-Oct4 partnerships and demonstrates that the cooperativity correlates with the efficiency in producing induced pluripotent stem cells. Our results suggest selective Sox-Oct partnerships in genome regulation and provide a toolset to study protein cooperation on DNA.

AB - Several Sox-Oct transcription factor (TF) combinations have been shown to cooperate on diverse enhancers to determine cell fates. Here, we developed a method to quantify biochemically the Sox-Oct cooperation and assessed the pairing of the high-mobility group (HMG) domains of 11 Sox TFs with Oct4 on a series of composite DNA elements. This way, we clustered Sox proteins according to their dimerization preferences illustrating that Sox HMG domains evolved different propensities to cooperate with Oct4. Sox2, Sox14, Sox21 and Sox15 strongly cooperate on the canonical element but compete with Oct4 on a recently discovered compressed element. Sry also cooperates on the canonical element but binds additively to the compressed element. In contrast, Sox17 and Sox4 cooperate more strongly on the compressed than on the canonical element. Sox5 and Sox18 show some cooperation on both elements, whereas Sox8 and Sox9 compete on both elements. Testing rationally mutated Sox proteins combined with structural modeling highlights critical amino acids for differential Sox-Oct4 partnerships and demonstrates that the cooperativity correlates with the efficiency in producing induced pluripotent stem cells. Our results suggest selective Sox-Oct partnerships in genome regulation and provide a toolset to study protein cooperation on DNA.

UR - http://www.scopus.com/inward/record.url?scp=84858329386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858329386&partnerID=8YFLogxK

U2 - 10.1093/nar/gks153

DO - 10.1093/nar/gks153

M3 - Article

VL - 40

SP - 4933

EP - 4941

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -