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Related Concept Videos

Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Position-effect Variegation02:32

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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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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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Histone Modification02:32

Histone Modification

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
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Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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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.
Writers
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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
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Non-canonical bivalent H3K4me3K9me3 recognition by Spindlin1/C11orf84 complex.

Yongming Du1, Chengmin Qian1

  • 1School of Biomedical Sciences, The University of Hong Kong, Pok Fu Lam, Hong Kong.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|January 29, 2022
PubMed
Summary

Bivalent chromatin marks, like H3K4me3 and H3K27me3, control gene expression. Our study shows the Spindlin1/C11orf84 complex recognizes a novel bivalent mark (H3K4me3K9me3) to activate transcription.

Keywords:
C11orf84H3K4me3H3K9me3HP1Spindlin1bivalent domainstranscriptional regulation

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Area of Science:

  • Epigenetics and Gene Regulation
  • Chromatin Biology
  • Molecular Mechanisms of Transcription

Background:

  • Bivalent chromatin, marked by both active (H3K4me3) and repressive (H3K27me3) histone modifications, is crucial for developmental gene regulation in embryonic stem cells.
  • While bivalency's role in controlling gene transcription during development is recognized, the precise molecular mechanisms linking bivalent chromatin to transcriptional regulation remain largely unclear.
  • Previous research has identified various bivalent modifications beyond the canonical H3K4me3/H3K27me3 pair in both stem and differentiated cells.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying bivalent chromatin's role in transcriptional regulation.
  • To explore the function of the Spindlin1/C11orf84 complex in recognizing specific bivalent histone marks.
  • To test the hypothesis that Spindlin1/C11orf84-mediated recognition of H3K4me3K9me3 bivalency is a general mechanism for chromatin activation.

Main Methods:

  • Analysis of bivalent histone modifications in different cell types.
  • Biochemical assays to determine the binding preferences of the Spindlin1/C11orf84 complex.
  • Functional studies assessing the role of Spindlin1/C11orf84 in ribosomal RNA transcription.

Main Results:

  • The Spindlin1/C11orf84 complex specifically recognizes the non-canonical bivalent histone mark H3K4me3K9me3.
  • This recognition is essential for the timely transcription of ribosomal RNA (rRNA).
  • Evidence suggests this mechanism may facilitate the conversion of repressed chromatin to an active state.

Conclusions:

  • The Spindlin1/C11orf84 complex plays a critical role in transcriptional regulation through specific recognition of bivalent histone marks.
  • The H3K4me3K9me3 bivalent mark, recognized by Spindlin1/C11orf84, is important for rRNA gene activation.
  • This interaction presents a potential general mechanism for converting repressed chromatin to an active state, advancing our understanding of epigenetic regulation.