SATB1-mediated chromatin landscape in T cells

Ζελένκα, Τόμας; Spilianakis, Charalampos G.

doi:10.1080/19491034.2020.1775037

Cited by 25 publications

(31 citation statements)

References 147 publications

(256 reference statements)

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“…We have identified SATB1, a factor exhibiting enriched occupancy at gene promoters and enhancers involved in long-range chromatin interactions. SATB1 has been attributed to many biological roles, mostly during T cell development (Zelenka and Spilianakis, 2020), but it also regulates the function of cell types such as the epidermis (Fessing et al, 2011) and neurons (Balamotis et al, 2012; Denaxa et al, 2012). Moreover, SATB1 is also overexpressed in a wide array of cancers and is positively associated with increased tumour size, metastasis, tumour progression, poor prognosis and reduced overall survival (Sunkara et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The 3D enhancer network of the developing T cell genome is controlled by SATB1

Ζελένκα

Klonizakis

Tsoukatou

et al. 2021

Preprint

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SummaryMechanisms of tissue-specific gene expression regulation via spatial coordination of gene promoters and distal regulatory elements are still poorly understood. We investigated the 3D genome organization of developing murine T cells and identified SATB1, a tissue-specific genome organizer, enriched at the anchors of promoter-enhancer chromatin loops. We assessed the function of SATB1 in T cell chromatin organization and compared it to the conventional genome organizer CTCF. SATB1 builds a more refined layer of genome organization upon a CTCF scaffold. To understand the regulatory implications of SATB1 loopscape structure, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals which suffered from autoimmunity. We aimed to identify molecular mechanisms responsible for the deregulation of the immune system in Satb1 cKO animals. H3K27ac HiChIP and Hi-C experiments indicated that SATB1 primarily mediates promoter-enhancer loops affecting master regulator genes (such as Bcl6), the T cell receptor locus and adhesion molecule genes, collectively being critical for cell lineage specification and immune system homeostasis. Our findings unravel the function of a tissue-specific factor that controls transcription programs, via spatial chromatin arrangements complementary to the chromatin structure imposed by ubiquitously expressed genome organizers.

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Section: Introductionmentioning

confidence: 99%

The 3D enhancer network of the developing T cell genome is controlled by SATB1

Ζελένκα

Klonizakis

Tsoukatou

et al. 2021

Preprint

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“…After basic pre-processing, droplets were identified in each cell for each time point Structure of SATB1 and the use of predictors SATB1 domains used in Fig. 1a were previously described 20 . The prediction of IDR regions in Fig.…”

Section: Live Cell Microscopymentioning

confidence: 99%

“…In this work, we focused on the physiological and pathological implications of SATB1's phase transitions. Apart from its physiological roles in T cells, where it is predominantly expressed 20 , SATB1 has been largely studied in the context of various cancers [21][22][23] . Apart of its function as a tissue-specific genome organizer 19,24 , it also modulates nuclear architecture by recruiting chromatin modifying protein complexes 25,26 .…”

Section: Introductionmentioning

confidence: 99%

A novel SATB1 protein isoform with different biophysical properties

Ζελένκα

Tzerpos

Panagopoulos

et al. 2021

Preprint

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Intracellular space is demarcated into functional membraneless organelles and nuclear bodies via the process of phase separation. Phase transitions are involved in many functions linked to such bodies as well as in gene expression regulation and other cellular processes. In this work we describe how the genome organizer SATB1 utilizes its prion-like domains to undergo phase transitions. We have identified two SATB1 isoforms with distinct biophysical behavior and showed how phosphorylation and interaction with nuclear RNA, impact their phase transitions. Moreover, we show that SATB1 is associated with transcription and splicing, both of which evinced deregulation in Satb1 knockout mice. Thus, the tight regulation of different SATB1 isoforms levels and their post-translational modifications are imperative for SATB1's physiological roles in T cell development while their deregulation may be linked to disorders such as cancer.

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“…For the higher-order loop structure formation, tetramerization is essential. The DNA-binding activity of the N-terminal domain is likely due to the CUT-like domain in it (Zelenka and Spilianakis, 2020 ). The CUT domain determines the affinity to DNA, and the homeodomain imparts specificity of interaction (Yamasaki et al, 2007 ).…”

Section: An Overview Of Scaffold/matrix Attachment Region-binding Promentioning

confidence: 99%

Chemical Decorations of “MARs” Residents in Orchestrating Eukaryotic Gene Regulation

Roychowdhury

Chattopadhyay

2020

Front. Cell Dev. Biol.

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Genome organization plays a crucial role in gene regulation, orchestrating multiple cellular functions. A meshwork of proteins constituting a three-dimensional (3D) matrix helps in maintaining the genomic architecture. Sequences of DNA that are involved in tethering the chromatin to the matrix are called scaffold/matrix attachment regions (S/MARs), and the proteins that bind to these sequences and mediate tethering are termed S/MAR-binding proteins (S/MARBPs). The regulation of S/MARBPs is important for cellular functions and is altered under different conditions. Limited information is available presently to understand the structure–function relationship conclusively. Although all S/MARBPs bind to DNA, their context- and tissue-specific regulatory roles cannot be justified solely based on the available information on their structures. Conformational changes in a protein lead to changes in protein–protein interactions (PPIs) that essentially would regulate functional outcomes. A well-studied form of protein regulation is post-translational modification (PTM). It involves disulfide bond formation, cleavage of precursor proteins, and addition or removal of low-molecular-weight groups, leading to modifications like phosphorylation, methylation, SUMOylation, acetylation, PARylation, and ubiquitination. These chemical modifications lead to varied functional outcomes by mechanisms like modifying DNA–protein interactions and PPIs, altering protein function, stability, and crosstalk with other PTMs regulating subcellular localizations. S/MARBPs are reported to be regulated by PTMs, thereby contributing to gene regulation. In this review, we discuss the current understanding, scope, disease implications, and future perspectives of the diverse PTMs regulating functions of S/MARBPs.

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SATB1-mediated chromatin landscape in T cells

Cited by 25 publications

References 147 publications

The 3D enhancer network of the developing T cell genome is controlled by SATB1

The 3D enhancer network of the developing T cell genome is controlled by SATB1

A novel SATB1 protein isoform with different biophysical properties

Chemical Decorations of “MARs” Residents in Orchestrating Eukaryotic Gene Regulation

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