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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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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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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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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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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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A Chromatin Assay for Human Brain Tissue
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Accesibilidad de la cromatina durante el desarrollo neurológico humano del primer trimestre

Camiel C A Mannens1, Lijuan Hu1, Peter Lönnerberg1

  • 1Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden.

Nature
|May 1, 2024
PubMed
Resumen
Este resumen es generado por máquina.

Este estudio mapea la accesibilidad de la cromatina y la expresión génica en el cerebro humano en desarrollo durante el desarrollo temprano. Revela los mecanismos reguladores de genes e identifica tipos específicos de neuronas vulnerables a las mutaciones de los trastornos del desarrollo neurológico.

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Área de la Ciencia:

  • La neurociencia
  • La genómica
  • Biología del desarrollo

Sus antecedentes:

  • El desarrollo del cerebro humano implica una regulación genética compleja a través de factores de transcripción y accesibilidad a la cromatina.
  • Los estudios anteriores carecían de atlas completos de accesibilidad de la cromatina para todo el cerebro en desarrollo, especialmente en el primer trimestre.
  • Los atlas de expresión génica de una sola célula existen, pero los datos de accesibilidad de la cromatina emparejada en todo el cerebro en desarrollo son limitados.

Objetivo del estudio:

  • Crear un atlas completo de la accesibilidad de la cromatina y la expresión génica emparejada en todo el cerebro humano en desarrollo durante el primer trimestre.
  • Identificar los elementos reguladores de genes y sus genes diana implicados en el desarrollo neurológico temprano.
  • Investigar los fundamentos genéticos de los trastornos del desarrollo neurológico vinculando las variaciones genéticas a los elementos reguladores.

Principales métodos:

  • Datos multiómicos generados (accesibilidad a la cromatina y expresión génica) del cerebro humano en desarrollo (6-13 semanas después de la concepción).
  • Se definieron 135 grupos celulares distintos y se vincularon elementos cis-reguladores a la expresión génica.
  • Empleó redes neuronales convolucionales para identificar sitios de unión del factor de transcripción y analizó polimorfismos de nucleótido único asociados a enfermedades.

Principales resultados:

  • Mapa de la accesibilidad de la cromatina y la expresión génica en todo el cerebro humano en desarrollo en el primer trimestre.
  • Se observó un aumento en las regiones accesibles con edad de desarrollo y diferenciación neuronal.
  • Se identificaron subtipos neuronales específicos, como las neuronas GABAérgicas del cerebro medio, vulnerables a las mutaciones relacionadas con el trastorno depresivo mayor.

Conclusiones:

  • Proporciona una referencia detallada para los mecanismos reguladores de genes en el desarrollo temprano del cerebro humano.
  • Enlaza elementos reguladores específicos y factores de transcripción con la especificación del subtipo neuronal.
  • Destaca el potencial del mapeo de la accesibilidad de la cromatina para comprender los trastornos del desarrollo neurológico y identificar poblaciones celulares vulnerables.