POZ/BTB and AT hook containing zinc finger 1 (PATZ1) suppresses differentiation and regulates metabolism in human embryonic stem cells

Huang, Min; Liao, Xiaohua; Wang, Xuepeng; Qian, Yiwei; Zhang, Wensheng; Chen, Guokai; Wu, Qiang

doi:10.7150/ijbs.83927

Cited by 2 publications

References 52 publications

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Regulatory plasticity of the human genome

Srivastava,

Ovcharenko

2024

Preprint

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Evolutionary turnover in non-coding regions has driven phenotypic divergence during past speciation events and continues to facilitate environmental adaptation through variants. We used a deep learning model to identify the substrates of regulatory turnover using genome wide mutations mimicking three evolutionary pathways: recent history (human-chimp substitutions), modern population (human population variation), and mutational susceptibility (random mutations). We observed enhancer turnover in approximately 6% of the whole genome, with more than 80% of the novel activity arising from repurposing of enhancers between cell-types. Frequency of turnover in a cell-type is remarkably similar across the three pathways, despite only ~19% overlap in the source regions. The enhancers predisposed to turnover display reduced evolutionary constraints and are depleted in GWAS variants. Most of these occur within 100kb of a gene, with the highest turnover occurring near neurodevelopmental genes including CNTNAP2, NPAS3, and AUTS2. Flanking enhancers of these genes undergo high turnover irrespective of the mutational model pathway, suggesting a high plasticity in neurocognitive evolution. Based on susceptibility to random mutations, these enhancers were identified as vulnerable by nature and feature a higher abundance of cell type-specific transcription factor binding sites (TFBSs). Our findings suggest that enhancer repurposing within vulnerable loci drives regulatory innovation while keeping the core regulatory networks intact.

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Regulatory plasticity of the human genome

Srivastava,

Ovcharenko

2024

Preprint

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Binding to the Other Side: The AT-Hook DNA-Binding Domain Allows Nuclear Factors to Exploit the DNA Minor Groove

Battista,

Fedele,

Secco

et al. 2024

IJMS

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The “AT-hook” is a peculiar DNA-binding domain that interacts with DNA in the minor groove in correspondence to AT-rich sequences. This domain has been first described in the HMGA protein family of architectural factors and later in various transcription factors and chromatin proteins, often in association with major groove DNA-binding domains. In this review, using a literature search, we identified about one hundred AT-hook-containing proteins, mainly chromatin proteins and transcription factors. After considering the prototypes of AT-hook-containing proteins, the HMGA family, we review those that have been studied in more detail and that have been involved in various pathologies with a particular focus on cancer. This review shows that the AT-hook is a domain that gives proteins not only the ability to interact with DNA but also with RNA and proteins. This domain can have enzymatic activity and can influence the activity of the major groove DNA-binding domain and chromatin docking modules when present, and its activity can be modulated by post-translational modifications. Future research on the function of AT-hook-containing proteins will allow us to better decipher their function and contribution to the different pathologies and to eventually uncover their mutual influences.

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POZ/BTB and AT hook containing zinc finger 1 (PATZ1) suppresses differentiation and regulates metabolism in human embryonic stem cells

Cited by 2 publications

References 52 publications

Regulatory plasticity of the human genome

Regulatory plasticity of the human genome

Binding to the Other Side: The AT-Hook DNA-Binding Domain Allows Nuclear Factors to Exploit the DNA Minor Groove

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