Asymmetric conservation within pairs of co-occurred motifs mediates weak direct binding of transcription factors in chip-seq data

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Asymmetric conservation within pairs of co-occurred motifs mediates weak direct binding of transcription factors in chip-seq data. / Levitsky, Victor; Oshchepkov, Dmitry; Zemlyanskaya, Elena et al.

In: International Journal of Molecular Sciences, Vol. 21, No. 17, 6023, 21.08.2020, p. 1-22.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{053d568f497f453387fcbd835a50533a,

title = "Asymmetric conservation within pairs of co-occurred motifs mediates weak direct binding of transcription factors in chip-seq data",

abstract = "(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. (2) Methods: We applied the motifs co-occurrence tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for the prediction of asymmetric CEs with one of the participating motifs possessing higher conservation than another does. (3) Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from the ETS (E26 Transformation Specific) family. (4) Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq.",

keywords = "Chromatin immunoprecipitation with massively parallel sequencing, Classification of transcription factors, Composite elements, Cooperative binding of transcription factors, Direct binding of transcription factors, ETS transcription factor family, Motifs conservation, Overlap of motifs, Transcription factors binding sites prediction",

author = "Victor Levitsky and Dmitry Oshchepkov and Elena Zemlyanskaya and Tatyana Merkulova",

year = "2020",

month = aug,

day = "21",

doi = "10.3390/ijms21176023",

language = "English",

volume = "21",

pages = "1--22",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "17",

}

RIS

TY - JOUR

T1 - Asymmetric conservation within pairs of co-occurred motifs mediates weak direct binding of transcription factors in chip-seq data

AU - Levitsky, Victor

AU - Oshchepkov, Dmitry

AU - Zemlyanskaya, Elena

AU - Merkulova, Tatyana

PY - 2020/8/21

Y1 - 2020/8/21

N2 - (1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. (2) Methods: We applied the motifs co-occurrence tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for the prediction of asymmetric CEs with one of the participating motifs possessing higher conservation than another does. (3) Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from the ETS (E26 Transformation Specific) family. (4) Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq.

AB - (1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. (2) Methods: We applied the motifs co-occurrence tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for the prediction of asymmetric CEs with one of the participating motifs possessing higher conservation than another does. (3) Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from the ETS (E26 Transformation Specific) family. (4) Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq.

KW - Chromatin immunoprecipitation with massively parallel sequencing

KW - Classification of transcription factors

KW - Composite elements

KW - Cooperative binding of transcription factors

KW - Direct binding of transcription factors

KW - ETS transcription factor family

KW - Motifs conservation

KW - Overlap of motifs

KW - Transcription factors binding sites prediction

UR - http://www.scopus.com/inward/record.url?scp=85089700228&partnerID=8YFLogxK

U2 - 10.3390/ijms21176023

DO - 10.3390/ijms21176023

M3 - Article

C2 - 32825662

AN - SCOPUS:85089700228

VL - 21

SP - 1

EP - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 17

M1 - 6023

ER -

ID: 25296829