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Spatial Organization of Chromatin: Transcriptional Control of Adaptive Immune Cell Development

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.633825

Keywords

chromatin organization; cis-regulatory interactions; gene regulatory networks; phase-separation; B and T cell development

Categories

Funding

  1. Department of Science and Technology (DST-SERB) [CRG/2018/002753]
  2. Department of Biotechnology [BT/PR32456/BRB/10/1785/2019]
  3. National Institutes of Health (NIH) [AI00880, AI09599, AI102853]

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The higher-order spatial organization of the genome, including chromatin compartments, self-associating domains, and regulatory loops, plays important roles in gene regulation. Chromatin regulatory loops, facilitated by CTCF and the cohesin machinery, bring enhancers and transcription factors in close proximity to target gene promoters, thereby regulating gene expression. Progress has been made in understanding how these loops are assembled and how they impact gene expression patterns.
Higher-order spatial organization of the genome into chromatin compartments (permissive and repressive), self-associating domains (TADs), and regulatory loops provides structural integrity and offers diverse gene regulatory controls. In particular, chromatin regulatory loops, which bring enhancer and associated transcription factors in close spatial proximity to target gene promoters, play essential roles in regulating gene expression. The establishment and maintenance of such chromatin loops are predominantly mediated involving CTCF and the cohesin machinery. In recent years, significant progress has been made in revealing how loops are assembled and how they modulate patterns of gene expression. Here we will discuss the mechanistic principles that underpin the establishment of three-dimensional (3D) chromatin structure and how changes in chromatin structure relate to alterations in gene programs that establish immune cell fate.

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