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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors02:16

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Video Experimental Relacionado

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Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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Published on: October 30, 2015

Los elementos vinculantes del CTCF median el control de la recombinación V(D) J.

Chunguang Guo1, Hye Suk Yoon, Andrew Franklin

  • 1Howard Hughes Medical Institute, The Children's Hospital, The Immune Disease Institute, Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.

Nature
|September 13, 2011
PubMed
Resumen

Los investigadores identificaron una nueva región reguladora, IGCR1, crucial para la recombinación de inmunoglobulina de cadena pesada (IgH) V (D) J en ratones. Esta región asegura el desarrollo adecuado de las células B y la diversidad de anticuerpos mediante el control de la reorganización del segmento genético.

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Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization

Published on: February 3, 2013

Área de la Ciencia:

  • Inmunología Inmunología.
  • Biología Molecular Biología Molecular
  • Genética La genética.

Sus antecedentes:

  • Los linfocitos B en desarrollo ensamblan exones de región variable de cadena pesada de inmunoglobulina (IgH) de los segmentos de genes V, D y J.
  • El locus Igh del ratón de 2,7 megabases requiere una regulación precisa de la recombinación V(D) J para repertorios de anticuerpos específicos y diversos.

Objetivo del estudio:

  • Identificar y caracterizar una nueva región reguladora dentro del locus Igh del ratón involucrado en la recombinación V(D) J.
  • Aclarar el papel funcional de esta región en el desarrollo de las células B y la formación del repertorio de anticuerpos.

Principales métodos:

  • Identificación de la región de control intergenico 1 (IGCR1) entre los grupos de genes V (H) y D en ratones.
  • Análisis funcional utilizando elementos de unión de factor de aislamiento / aislamiento CTCF y mediación de bucles Igh con potenciadores distantes.

Principales resultados:

  • IGCR1 inhibe la transcripción y el reordenamiento de los segmentos de genes D(H) -proximal V(H) mientras promueve el reordenamiento de los segmentos distales V(H).
  • IGCR1 asegura la recombinación ordenada de V, H, D, J, H, evitando las uniones incorrectas en los timocitos y regulando la retroalimentación.
  • IGCR1 es esencial para la regulación de la retroalimentación y la exclusión alélica de la recombinación proximal V ((H) a DJ ((H).

Conclusiones:

  • IGCR1 es una región reguladora crítica para la recombinación de inmunoglobulina de cadena pesada V (((D) J.
  • IGCR1 juega un papel clave en el desarrollo normal de las células B, el equilibrio del repertorio de anticuerpos y la recombinación específica del linaje.
  • El estudio destaca una función novedosa para la proteína CTCF en la regulación del locus Igh.