Remodeling the chromatin landscape in T lymphocytes by a division of labor among transcription factors

Vahedi, Golnaz

doi:10.1111/imr.12942

Cited by 8 publications

(3 citation statements)

References 162 publications

(340 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mammalian genomes are characterized by their higher order of chromatin structure in the 3D nuclear space, which is crucial for gene expression and the epigenetic regulation governing thymic development. The differentiation of several T cell lineages depends on multiple global and tissue specific transcription factors (histone modifiers and chromatin remodelers) controlling spatiotemporal gene expression (183)(184)(185). These proteins in association with cis-regulatory regions (enhancer and promoter elements) along the genome, define the dynamic conformation of chromatin.…”

Section: Discussionmentioning

confidence: 99%

3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells

2022

View full text Add to dashboard Cite

In the heart of innate and adaptive immunity lies the proper spatiotemporal development of several immune cell lineages. Multiple studies have highlighted the necessity of epigenetic and transcriptional regulation in cell lineage specification. This mode of regulation is mediated by transcription factors and chromatin remodelers, controlling developmentally essential gene sets. The core of transcription and epigenetic regulation is formulated by different epigenetic modifications determining gene expression. Apart from “classic” epigenetic modifications, 3D chromatin architecture is also purported to exert fundamental roles in gene regulation. Chromatin conformation both facilitates cell-specific factor binding at specified regions and is in turn modified as such, acting synergistically. The interplay between global and tissue-specific protein factors dictates the epigenetic landscape of T and innate lymphoid cell (ILC) lineages. The expression of global genome organizers such as CTCF, YY1, and the cohesin complexes, closely cooperate with tissue-specific factors to exert cell type-specific gene regulation. Special AT-rich binding protein 1 (SATB1) is an important tissue-specific genome organizer and regulator controlling both long- and short-range chromatin interactions. Recent indications point to SATB1’s cooperation with the aforementioned factors, linking global to tissue-specific gene regulation. Changes in 3D genome organization are of vital importance for proper cell development and function, while disruption of this mechanism can lead to severe immuno-developmental defects. Newly emerging data have inextricably linked chromatin architecture deregulation to tissue-specific pathophysiological phenotypes. The combination of these findings may shed light on the mechanisms behind pathological conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells

2022

View full text Add to dashboard Cite

show abstract

“…A large number of key lineage TF and protein cofactors in B/T lymphocyte development have been proposed to mediate chromatin reorganization and DNA looping as recently reviewed (77,145,(181)(182)(183), although functional validations and mechanistic insights of their proposed architectural function are often missing. Below, we discuss some of the beststudied examples: Special AT-rich binding protein 1 (SATB1) is a T cell enriched transcription/epigenetic factor critical for thymocyte development and differentiation.…”

Section: Lineage-specific Transcription Factorsmentioning

confidence: 99%

Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies

2021

View full text Add to dashboard Cite

Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.

show abstract

“…High order chromatin folding as well as its organization within the nuclear space are considered as an important regulator of gene expression and nuclear functions. In particular, during lymphopoiesis, spatial nuclear repositioning of different immune genes can be directly linked to their expression while deregulation of the chromatin architecture can be associated with immunerelated diseases and cancer (1)(2)(3)(4)(5)(6)(7)(8)(9). T-cell lineage specification remains a powerful developmental model system to study cis-or trans-genomic interactions and gene relocalization, since in most cases these movements can be linked to an immunological response (3,10).…”

Section: Introductionmentioning

confidence: 99%

Single-cell detection of primary transcripts, their genomic loci and nuclear factors by 3D immuno-RNA/DNA FISH in T cells

2023

View full text Add to dashboard Cite

Over the past decades, it has become increasingly clear that higher order chromatin folding and organization within the nucleus is involved in the regulation of genome activity and serves as an additional epigenetic mechanism that modulates cellular functions and gene expression programs in diverse biological processes. In particular, dynamic allelic interactions and nuclear locations can be of functional importance during the process of lymphoid differentiation and the regulation of immune responses. Analyses of the proximity between chromatin and/or nuclear regions can be performed on populations of cells with high-throughput sequencing approaches such as chromatin conformation capture (“3C”-based) or DNA adenine methyltransferase identification (DamID) methods, or, in individual cells, by the simultaneous visualization of genomic loci, their primary transcripts and nuclear compartments within the 3-dimensional nuclear space using Fluorescence In Situ Hybridization (FISH) and immunostaining. Here, we present a detailed protocol to simultaneously detect nascent RNA transcripts (3D RNA FISH), their genomic loci (3D DNA FISH) and/or their chromosome territories (CT paint DNA FISH) combined with the antibody-based detection of various nuclear factors (immunofluorescence). We delineate the application and effectiveness of this robust and reproducible protocol in several murine T lymphocyte subtypes (from differentiating thymic T cells, to activated splenic and peripheral T cells) as well as other murine cells, including embryonic stem cells, B cells, megakaryocytes and macrophages.

show abstract

Remodeling the chromatin landscape in T lymphocytes by a division of labor among transcription factors

Cited by 8 publications

References 162 publications

3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells

3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells

Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies

Single-cell detection of primary transcripts, their genomic loci and nuclear factors by 3D immuno-RNA/DNA FISH in T cells

Contact Info

Product

Resources

About