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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

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Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
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Chromatin Position Affects Gene Expression02:35

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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Co-activators and Co-repressors02:04

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Spreading of Chromatin Modifications02:25

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Decoding Gene Responsiveness to Synthetic Chromatin Reader-Actuators with Multi-Modal Epigenomic Profiling.

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    Synthetic reader-actuators reveal that specific chromatin signatures, beyond H3K27me3, dictate gene inducibility in differentiated cells, highlighting retained regulatory plasticity.

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    Area of Science:

    • Epigenetics and Gene Regulation
    • Cancer Cell Biology
    • Chromatin Biology

    Background:

    • Cell identity relies on chromatin states encoding gene regulatory memory.
    • Understanding how chromatin context affects inducibility in differentiated cells is crucial.

    Purpose of the Study:

    • To investigate how chromatin context influences gene inducibility in differentiated cells using synthetic reader-actuators (SRAs).
    • To dissect inducible chromatin features in their native genomic context.

    Main Methods:

    • Engineered synthetic reader-actuators (SRAs) containing the polycomb chromodomain (PCD) were employed.
    • Chromatin immunoprecipitation sequencing (ChIP-seq) mapped PCD-fusion occupancy.
    • RNA sequencing (RNA-seq) identified gene activation patterns.
    • Machine learning models (MLM) predicted PCD-fusion binding.

    Main Results:

    • PCD-fusion binding was predicted by H3K27me3, H4K20me1, or H3K36me3 enrichment at enhancers and chromatin transition zones.
    • Genes with PCD-fusion enriched enhancers that were SRA-induced showed specific promoter features.
    • These features included bivalent histone modifications and enrichment of transcriptional repressors REST and MTA1.

    Conclusions:

    • SRA responsiveness depends on a specific chromatin signature beyond H3K27me3.
    • Epigenetically repressed regions in differentiated cells retain regulatory plasticity.
    • SRAs are powerful tools for dissecting inducible chromatin features.