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Chromatin Modification in iPS Cells01:32

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Related Experiment Video

Updated: Jan 11, 2026

Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
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Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq

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METTL3 Uncouples Chromatin Accessibility from Transcription during Retinal Development.

Jing Xu, Yuanhao Huang, Zhaowei Han

    Biorxiv : the Preprint Server for Biology
    |November 19, 2025
    PubMed
    Summary
    This summary is machine-generated.

    Methyltransferase-like 3 (METTL3) is crucial for retinal development by regulating RNA metabolism. Its epitranscriptomic function impacts retinal progenitor cell differentiation and gene stability via m6A modification.

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    Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation

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    Area of Science:

    • Developmental Biology
    • Epitranscriptomics
    • RNA Metabolism

    Background:

    • Methyltransferase-like 3 (METTL3) is a key regulator of RNA metabolism.
    • Its roles in tissue development, particularly in the retina, are not well understood.
    • Retinal progenitor cell (RPC) differentiation is a complex process involving precise gene regulation.

    Purpose of the Study:

    • To investigate the genomic and epitranscriptomic functions of METTL3 in retinal development.
    • To dissect the role of METTL3 in retinal progenitor cell differentiation using 3D retinal organoids.
    • To understand the interplay between METTL3, m6A modification, and gene regulation during retinal development.

    Main Methods:

    • Utilized embryonic stem cell-derived 3D retinal organoids to model retinal development.
    • Integrated multi-omics approaches: m6A profiling (GLORI), ChIP-seq, CUT&RUN, ATAC-seq, and dCas13b-FTO for targeted m6A engineering.
    • Employed a degron-based METTL3 degradation strategy and protein-RNA interaction profiling.

    Main Results:

    • Loss of METTL3 disrupted retinal anlage formation in vitro.
    • m6A modification at the Six3 3'UTR was found to govern gene stability.
    • METTL3 loss altered histone modifications and chromatin accessibility, but direct chromatin targets showed limited transcriptional correlation, revealing a METTL3-Ythdf1 protein-RNA axis.

    Conclusions:

    • METTL3-dependent m6A modification is a critical epitranscriptomic layer in retinal development.
    • Established a novel genomic paradigm where chromatin accessibility can diverge from transcriptional output.
    • Highlights the importance of epitranscriptomic regulation in developmental processes.