Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins
KRAB C2H2 zinc finger proteins (KZNFs) are the largest and most diverse family of human transcription factors, likely due to diversifying selection driven by novel endogenous retroelements (EREs), but the vast majority lack binding motifs or functional data. Two recent studies analyzed a majority of...
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doaj-d4d7b76d60014ed784c03e947222da922021-07-02T02:30:58ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362018-01-018121922910.1534/g3.117.30029620Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger ProteinsMarjan BarazandehSamuel A. LambertMihai AlbuTimothy R. HughesKRAB C2H2 zinc finger proteins (KZNFs) are the largest and most diverse family of human transcription factors, likely due to diversifying selection driven by novel endogenous retroelements (EREs), but the vast majority lack binding motifs or functional data. Two recent studies analyzed a majority of the human KZNFs using either ChIP-seq (60 proteins) or ChIP-exo (221 proteins) in the same cell type (HEK293). The ChIP-exo paper did not describe binding motifs, however. Thirty-nine proteins are represented in both studies, enabling the systematic comparison of the data sets presented here. Typically, only a minority of peaks overlap, but the two studies nonetheless display significant similarity in ERE binding for 32/39, and yield highly similar DNA binding motifs for 23 and related motifs for 34 (MoSBAT similarity score >0.5 and >0.2, respectively). Thus, there is overall (albeit imperfect) agreement between the two studies. For the 242 proteins represented in at least one study, we selected a highest-confidence motif for each protein, utilizing several motif-derivation approaches, and evaluating motifs within and across data sets. Peaks for the majority (158) are enriched (96% with AUC >0.6 predicting peak vs. nonpeak) for a motif that is supported by the C2H2 “recognition code,” consistent with intrinsic sequence specificity driving DNA binding in cells. An additional 63 yield motifs enriched in peaks, but not supported by the recognition code, which could reflect indirect binding. Altogether, these analyses validate both data sets, and provide a reference motif set with associated quality metrics.http://g3journal.org/lookup/doi/10.1534/g3.117.300296KRAB C2H2 zinc finger proteinsendogenous retroelementsDNA-binding motifChIP-seqC2H2 recognition code |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marjan Barazandeh Samuel A. Lambert Mihai Albu Timothy R. Hughes |
spellingShingle |
Marjan Barazandeh Samuel A. Lambert Mihai Albu Timothy R. Hughes Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins G3: Genes, Genomes, Genetics KRAB C2H2 zinc finger proteins endogenous retroelements DNA-binding motif ChIP-seq C2H2 recognition code |
author_facet |
Marjan Barazandeh Samuel A. Lambert Mihai Albu Timothy R. Hughes |
author_sort |
Marjan Barazandeh |
title |
Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins |
title_short |
Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins |
title_full |
Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins |
title_fullStr |
Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins |
title_full_unstemmed |
Comparison of ChIP-Seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins |
title_sort |
comparison of chip-seq data and a reference motif set for human krab c2h2 zinc finger proteins |
publisher |
Oxford University Press |
series |
G3: Genes, Genomes, Genetics |
issn |
2160-1836 |
publishDate |
2018-01-01 |
description |
KRAB C2H2 zinc finger proteins (KZNFs) are the largest and most diverse family of human transcription factors, likely due to diversifying selection driven by novel endogenous retroelements (EREs), but the vast majority lack binding motifs or functional data. Two recent studies analyzed a majority of the human KZNFs using either ChIP-seq (60 proteins) or ChIP-exo (221 proteins) in the same cell type (HEK293). The ChIP-exo paper did not describe binding motifs, however. Thirty-nine proteins are represented in both studies, enabling the systematic comparison of the data sets presented here. Typically, only a minority of peaks overlap, but the two studies nonetheless display significant similarity in ERE binding for 32/39, and yield highly similar DNA binding motifs for 23 and related motifs for 34 (MoSBAT similarity score >0.5 and >0.2, respectively). Thus, there is overall (albeit imperfect) agreement between the two studies. For the 242 proteins represented in at least one study, we selected a highest-confidence motif for each protein, utilizing several motif-derivation approaches, and evaluating motifs within and across data sets. Peaks for the majority (158) are enriched (96% with AUC >0.6 predicting peak vs. nonpeak) for a motif that is supported by the C2H2 “recognition code,” consistent with intrinsic sequence specificity driving DNA binding in cells. An additional 63 yield motifs enriched in peaks, but not supported by the recognition code, which could reflect indirect binding. Altogether, these analyses validate both data sets, and provide a reference motif set with associated quality metrics. |
topic |
KRAB C2H2 zinc finger proteins endogenous retroelements DNA-binding motif ChIP-seq C2H2 recognition code |
url |
http://g3journal.org/lookup/doi/10.1534/g3.117.300296 |
work_keys_str_mv |
AT marjanbarazandeh comparisonofchipseqdataandareferencemotifsetforhumankrabc2h2zincfingerproteins AT samuelalambert comparisonofchipseqdataandareferencemotifsetforhumankrabc2h2zincfingerproteins AT mihaialbu comparisonofchipseqdataandareferencemotifsetforhumankrabc2h2zincfingerproteins AT timothyrhughes comparisonofchipseqdataandareferencemotifsetforhumankrabc2h2zincfingerproteins |
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1721343186718162944 |