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  1. Article ; Online: G&D

    Zaret, Kenneth S

    Genes & development

    2023  Volume 37, Issue 1-2, Page(s) 63–68

    Language English
    Publishing date 2023-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.350444.123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2292: Show issues Location:
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    Zs.MG 54: Show issues

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  2. Article ; Online: Two ways to skin a new cell fate.

    Zaret, Kenneth S

    Developmental cell

    2022  Volume 58, Issue 1, Page(s) 1–2

    Abstract: To induce cell fate changes, do transcription factors engage open domains of chromatin or elicit chromatin opening in a pioneering fashion? In this issue of Developmental Cell, Delás et al. show that the same sonic hedgehog (Shh) inducing signal can ... ...

    Abstract To induce cell fate changes, do transcription factors engage open domains of chromatin or elicit chromatin opening in a pioneering fashion? In this issue of Developmental Cell, Delás et al. show that the same sonic hedgehog (Shh) inducing signal can yield different neural tube fates by either modality.
    MeSH term(s) Hedgehog Proteins/metabolism ; Cell Differentiation ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Neural Tube/metabolism ; Chromatin ; Gene Expression Regulation, Developmental
    Chemical Substances Hedgehog Proteins ; Transcription Factors ; Chromatin
    Language English
    Publishing date 2022-12-15
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2022.12.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Pioneer factors: roles and their regulation in development.

    Barral, Amandine / Zaret, Kenneth S

    Trends in genetics : TIG

    2023  Volume 40, Issue 2, Page(s) 134–148

    Abstract: Pioneer factors are a subclass of transcription factors that can bind and initiate opening of silent chromatin regions. Pioneer factors subsequently regulate lineage-specific genes and enhancers and, thus, activate the zygotic genome after fertilization, ...

    Abstract Pioneer factors are a subclass of transcription factors that can bind and initiate opening of silent chromatin regions. Pioneer factors subsequently regulate lineage-specific genes and enhancers and, thus, activate the zygotic genome after fertilization, guide cell fate transitions during development, and promote various forms of human cancers. As such, pioneer factors are useful in directed cell reprogramming. In this review, we define the structural and functional characteristics of pioneer factors, how they bind and initiate opening of closed chromatin regions, and the consequences for chromatin dynamics and gene expression during cell differentiation. We also discuss emerging mechanisms that modulate pioneer factors during development.
    MeSH term(s) Humans ; Chromatin ; Transcription Factors/genetics ; Cell Differentiation/genetics ; Cellular Reprogramming ; Zygote
    Chemical Substances Chromatin ; Transcription Factors
    Language English
    Publishing date 2023-11-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 619240-3
    ISSN 1362-4555 ; 0168-9525 ; 0168-9479
    ISSN (online) 1362-4555
    ISSN 0168-9525 ; 0168-9479
    DOI 10.1016/j.tig.2023.10.007
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  4. Article ; Online: Pioneer Transcription Factors Initiating Gene Network Changes.

    Zaret, Kenneth S

    Annual review of genetics

    2020  Volume 54, Page(s) 367–385

    Abstract: Pioneer transcription factors have the intrinsic biochemical ability to scan partial DNA sequence motifs that are exposed on the surface of a nucleosome and thus access silent genes that are inaccessible to other transcription factors. Pioneer factors ... ...

    Abstract Pioneer transcription factors have the intrinsic biochemical ability to scan partial DNA sequence motifs that are exposed on the surface of a nucleosome and thus access silent genes that are inaccessible to other transcription factors. Pioneer factors subsequently enable other transcription factors, nucleosome remodeling complexes, and histone modifiers to engage chromatin, thereby initiating the formation of an activating or repressive regulatory sequence. Thus, pioneer factors endow the competence for fate changes in embryonic development, are essential for cellular reprogramming, and rewire gene networks in cancer cells. Recent studies with reconstituted nucleosomes in vitro and chromatin binding in vivo reveal that pioneer factors can directly perturb nucleosome structure and chromatin accessibility in different ways. This review focuses on our current understanding of the mechanisms by which pioneer factors initiate gene network changes and will ultimately contribute to our ability to control cell fates at will.
    MeSH term(s) Animals ; Cellular Reprogramming/genetics ; Chromatin/genetics ; Embryonic Development/genetics ; Gene Regulatory Networks/genetics ; Histones/genetics ; Humans ; Nucleosomes/genetics ; Transcription Factors/genetics
    Chemical Substances Chromatin ; Histones ; Nucleosomes ; Transcription Factors
    Language English
    Publishing date 2020-09-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 207928-8
    ISSN 1545-2948 ; 0066-4170 ; 0066-4197
    ISSN (online) 1545-2948
    ISSN 0066-4170 ; 0066-4197
    DOI 10.1146/annurev-genet-030220-015007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Maintaining Transcriptional Specificity Through Mitosis.

    Ito, Kenji / Zaret, Kenneth S

    Annual review of genomics and human genetics

    2022  Volume 23, Page(s) 53–71

    Abstract: Virtually all cell types have the same DNA, yet each type exhibits its own cell-specific pattern of gene expression. During the brief period of mitosis, the chromosomes exhibit changes in protein composition and modifications, a marked condensation, and ... ...

    Abstract Virtually all cell types have the same DNA, yet each type exhibits its own cell-specific pattern of gene expression. During the brief period of mitosis, the chromosomes exhibit changes in protein composition and modifications, a marked condensation, and a consequent reduction in transcription. Yet as cells exit mitosis, they reactivate their cell-specific programs with high fidelity. Initially, the field focused on the subset of transcription factors that are selectively retained in, and hence bookmark, chromatin in mitosis. However, recent studies show that many transcription factors can be retained in mitotic chromatin and that, surprisingly, such retention can be due to nonspecific chromatin binding. Here, we review the latest studies focusing on low-level transcription via promoters, rather than enhancers, as contributing to mitotic memory, as well as new insights into chromosome structure dynamics, histone modifications, cell cycle signaling, and nuclear envelope proteins that together ensure the fidelity of gene expression through a round of mitosis.
    MeSH term(s) Chromatin/genetics ; Chromosomes/genetics ; Histone Code ; Humans ; Mitosis/genetics ; Transcription Factors/genetics
    Chemical Substances Chromatin ; Transcription Factors
    Language English
    Publishing date 2022-04-19
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2037670-4
    ISSN 1545-293X ; 1527-8204
    ISSN (online) 1545-293X
    ISSN 1527-8204
    DOI 10.1146/annurev-genom-121321-094603
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Diverse heterochromatin states restricting cell identity and reprogramming.

    McCarthy, Ryan L / Zhang, Jingchao / Zaret, Kenneth S

    Trends in biochemical sciences

    2023  Volume 48, Issue 6, Page(s) 513–526

    Abstract: Heterochromatin is defined as a chromosomal domain harboring repressive H3K9me2/3 or H3K27me3 histone modifications and relevant factors that physically compact the chromatin. Heterochromatin can restrict where transcription factors bind, providing a ... ...

    Abstract Heterochromatin is defined as a chromosomal domain harboring repressive H3K9me2/3 or H3K27me3 histone modifications and relevant factors that physically compact the chromatin. Heterochromatin can restrict where transcription factors bind, providing a barrier to gene activation and changes in cell identity. While heterochromatin thus helps maintain cell differentiation, it presents a barrier to overcome during efforts to reprogram cells for biomedical purposes. Recent findings have revealed complexity in the composition and regulation of heterochromatin, and shown that transiently disrupting the machinery of heterochromatin can enhance reprogramming. Here, we discuss how heterochromatin is established and maintained during development, and how our growing understanding of the mechanisms regulating H3K9me3 heterochromatin can be leveraged to improve our ability to direct changes in cell identity.
    MeSH term(s) Heterochromatin ; Histones/metabolism ; Chromatin ; Cell Differentiation ; Transcription Factors/metabolism
    Chemical Substances Heterochromatin ; Histones ; Chromatin ; Transcription Factors
    Language English
    Publishing date 2023-03-27
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2023.02.007
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  7. Article ; Online: Pioneering the chromatin landscape.

    Zaret, Kenneth S

    Nature genetics

    2018  Volume 50, Issue 2, Page(s) 167–169

    MeSH term(s) Chromatin ; Chromatin Assembly and Disassembly ; Epigenesis, Genetic ; Epigenomics
    Chemical Substances Chromatin
    Language English
    Publishing date 2018-01-26
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-017-0038-z
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  8. Article ; Online: The telomerase enzyme and liver renewal.

    Zaret, Kenneth S

    Nature

    2018  Volume 556, Issue 7700, Page(s) 181–182

    MeSH term(s) Liver ; Liver Regeneration ; Telomerase/genetics ; Telomere
    Chemical Substances Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2018-04-11
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-018-02684-w
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  9. Article ; Online: Erratum for Zaret, At the Revolution with Fred Sherman.

    Zaret, Kenneth S

    Molecular and cellular biology

    2017  Volume 37, Issue 5

    Language English
    Publishing date 2017-02-15
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00671-16
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  10. Article ; Online: Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2.

    Lerner, Jonathan / Katznelson, Andrew / Zhang, Jingchao / Zaret, Kenneth S

    Cell reports

    2023  Volume 42, Issue 7, Page(s) 112748

    Abstract: Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer factors access chromatin by assisted loading with other transcription ... ...

    Abstract Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer factors access chromatin by assisted loading with other transcription factors, the nucleosome-binding properties of pioneer factors enable them to initiate zygotic genome activation, embryonic development, and cellular reprogramming. To better understand nucleosome targeting in vivo, we assess whether pioneer factors FoxA1 and Sox2 target stable or unstable nucleosomes and find that they target DNase-resistant, stable nucleosomes, whereas HNF4A, a non-nucleosome binding factor, targets open, DNase-sensitive chromatin. Despite FOXA1 and SOX2 targeting similar proportions of DNase-resistant chromatin, using single-molecule tracking, we find that FOXA1 uses lower nucleoplasmic diffusion and longer residence times while SOX2 uses higher nucleoplasmic diffusion and shorter residence times to scan compact chromatin, while HNF4 scans compact chromatin much less efficiently. Thus, pioneer factors target compact chromatin through distinct processes.
    MeSH term(s) Chromatin ; Deoxyribonucleases/metabolism ; Nucleosomes ; Protein Binding ; Transcription Factors/metabolism ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; SOXB1 Transcription Factors/metabolism
    Chemical Substances Chromatin ; Deoxyribonucleases (EC 3.1.-) ; Nucleosomes ; Transcription Factors ; Hepatocyte Nuclear Factor 3-alpha ; SOXB1 Transcription Factors
    Language English
    Publishing date 2023-07-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112748
    Database MEDical Literature Analysis and Retrieval System OnLINE

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