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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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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.
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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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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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Expression Analysis of Mammalian Linker-histone Subtypes
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Dynamic changes in H1 subtype composition during epigenetic reprogramming.

Annalisa Izzo1,2, Céline Ziegler-Birling2, Peter W S Hill3,4

  • 1Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg, Germany.

The Journal of Cell Biology
|August 11, 2017
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Summary
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Distinct histone H1 subtypes dynamically change during early development, influencing chromatin remodeling essential for epigenetic reprogramming and cellular identity. These H1 proteins are key to totipotency and cell state establishment.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Developmental Biology

Background:

  • Histone H1 proteins are crucial for chromatin structure and gene regulation.
  • Mammals have multiple H1 subtypes with distinct roles.
  • Understanding H1 subtype dynamics during development is vital for deciphering epigenetic reprogramming.

Purpose of the Study:

  • To investigate the expression and function of H1 subtypes during key epigenetic reprogramming periods.
  • To analyze H1 subtype dynamics in early mouse embryos and developing germ cells.

Main Methods:

  • Generation of knockin mouse lines with tagged endogenous H1 subtypes.
  • Systematic study of H1 subtype expression and localization during development.

Main Results:

  • Dynamic changes in H1 subtype expression and localization correlate with chromatin remodeling.
  • Specific combinations of H1 subtypes characterize different preimplantation development stages.
  • H1 subtype abundance distinguishes male and female chromatin in developing germ cells.

Conclusions:

  • Distinct H1 subtypes play critical roles in mediating chromatin remodeling during epigenetic reprogramming.
  • H1 subtypes are essential for acquiring cellular totipotency and establishing specific cellular states.