An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos

Liu, Longqi; Leng, Lizhi; Liu, Chuanyu; Lu, Can‐Zhong; Yuan, Yue; Wu, Liang; Gong, Fei; Zhang, Shuoping; Wei, Xiaoyü; Wang, Mingyue; Zhao, Lei; Hu, Liang; Wang, Jian; Yang, Huanming; Zhu, Shida; Chen, Fang; Lu, Guangxiu; Shang, Zhouchun; Lin, Ge

doi:10.1038/s41467-018-08244-0

Cited by 90 publications

(117 citation statements)

References 50 publications

(72 reference statements)

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“…Second, we identify distinct clusters of TFs for which binding of the core motif is predicted by similar motifs shown to interact previously with those factors. For example, the NFY motif previously been reported to contain NFYB binding sites 49 . Additionally, we found that while binding of NFYA, NFYB, and factors with similar binding patterns is strongly predicted by the presence of canonical NFY motifs in the context, 5-mers similar to CCAAT/ATTGG but mismatched at one nucleotide also received high Grad-CAM scores ( Fig.…”

Section: Grad-cam Scores Give Insight Into Features Of Tf Bindingmentioning

confidence: 99%

Deep neural networks identify context-specific determinants of transcription factor binding affinity

Zheng

Lamkin

et al. 2020

Preprint

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Transcription factors (TFs) bind DNA by recognizing highly specific DNA sequence motifs, typically of length 6-12bp. A TF motif can occur tens of thousands of times in the human genome, but only a small fraction of those sites are actually bound. Despite the availability of genome-wide TF binding maps for hundreds of TFs, predicting whether a given motif occurrence is bound and identifying the influential context features remain challenging. Here we present a machine learning framework leveraging existing convolutional neural network architectures and state of the art model interpretation techniques to identify, visualize, and interpret context features most important for determining binding activity for a particular TF. We apply our framework to predict binding at motifs for 38 TFs in a lymphoblastoid cell line and achieve superior classification performance compared to existing frameworks. We compute importance scores for context regions at single base pair resolution and uncover known and novel determinants of TF binding. Finally, we demonstrate that important context bases are under increased purifying selection compared to nearby bases and are enriched in disease-associated variants identified by genome-wide association studies.

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Section: Grad-cam Scores Give Insight Into Features Of Tf Bindingmentioning

confidence: 99%

Deep neural networks identify context-specific determinants of transcription factor binding affinity

Zheng

Lamkin

et al. 2020

Preprint

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“…To address the first question, we set out to investigate the role of Pou5f3, Sox19b and Nanog in opening up chromatin. These transcription factors are maternally loaded, and have been shown to 6 be required for the activation of many zygotic genes [15,22,24]. Moreover, their motifs are enriched in the distal regions that increase in accessibility between 256-cell and oblong stage ( Figure S6).…”

Section: Pou5f3 Sox19b and Nanog Regulate Chromatin Accessibilitymentioning

confidence: 99%

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Pálfy

Schulze

Valen

et al. 2019

Preprint

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In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription.Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

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“…While a number of studies suggest that chromatin accessibility generally correlates with gene activity [4][5][6], others have suggested that this correlation is, at least globally, rather weak. For example, chromatin accessibility landscapes are broadly similar in cell types and tissues with different expression signatures, and in embryonic cells exposed to different transcription factor concentrations [2,7,8].…”

Section: Introductionmentioning

confidence: 99%

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

et al. 2020

View full text Add to dashboard Cite

In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remain poorly understood. Here, we generated chromatin accessibility maps with ATAC-seq from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hypertranscribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription. Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

show abstract

An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos

Cited by 90 publications

References 50 publications

Deep neural networks identify context-specific determinants of transcription factor binding affinity

Deep neural networks identify context-specific determinants of transcription factor binding affinity

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

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