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

Ζελένκα, Τόμας; Klonizakis, Antonios; Tsoukatou, Despina; Franzenburg, Sören; Tzerpos, Petros; Papamatheakis, Dionysios-Alexandros; Tzonevrakis, Ioannis-Rafail; Nikolaou, Christoforos; Plewczynski, Dariusz; Spilianakis, Charalampos G.

doi:10.1101/2021.07.09.451769

Cited by 5 publications

(20 citation statements)

References 128 publications

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“…2d). Similarly, the transcription of multiple genes was directly affected by SATB1 binding as we previously demonstrated 19 .…”

Section: Satb1 Co-localizes With Sites Of Active Transcriptionsupporting

confidence: 60%

“…Therefore, we reasoned that a more plausible hypothesis would be based on the regulation of alternative splicing. We should note that we have identified a binding site specific to the long SATB1 isoform 19 right at the extra exon of the long isoform (Fig. 6f), suggesting a potential autoregulatory role for the expression of the long SATB1 isoform.…”

Section: Modes Of Regulation Of Satb1 Phase Transitionsmentioning

confidence: 84%

“…The splicing efficiency was determined as the intron/exon coverage ratio and its changes as a difference between Satb1 cKO – WT intron/exon ratios. Moreover, the SATB1 binding sites’ dataset (GSE173446 19 ) was intersected with the junctions to search for a potential dependency of splicing on the SATB1 presence (Extended Data Fig. 2d).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we have identified the PrLD-containing protein SATB1 and investigated its function as a mediator of the 3D enhancer network in developing T cells 19 . In this work, we focused on the physiological and pathological implications of SATB1's phase transitions.…”

Section: Introductionmentioning

confidence: 99%

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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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“…2d). Similarly, the transcription of multiple genes was directly affected by SATB1 binding as we previously demonstrated 19 .…”

Section: Satb1 Co-localizes With Sites Of Active Transcriptionsupporting

confidence: 60%

Section: Modes Of Regulation Of Satb1 Phase Transitionsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel SATB1 protein isoform with different biophysical properties

Ζελένκα

Tzerpos

Panagopoulos

et al. 2021

Preprint

Self Cite

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“…Apart from the high number of inter-chromosomal interactions, we would like to highlight the limited number of short-range interaction pairs (<20 kbp), which emphasizes the high efficiency of the protocol. This protocol was successfully used to investigate the 3D enhancer network of murine thymocytes using SATB1 and CTCF HiChIP experiments in wild-type cells and Hi-C and H3K27ac HiChIP experiments in both wild-type and Satb1 fl/fl Cd4-Cre + cells [31].…”

Section: Expected Resultsmentioning

confidence: 99%

HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

Ζελένκα

Spilianakis

2021

MPs

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The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.

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A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells

Thomas

Martin

Bruzeau

et al. 2022

Preprint

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SATB1 (Special A-T rich Binding protein 1) is a cell type specific factor involved in chromatin remodeling events that participate in the regulation of the genetic network in developing T cells and neurons. In T cells, SATB1 is a key factor required for lineage commitment, VDJ recombination, development and maturation. In B cells, SATB1 is described as binding to the MARs-Eμ regions of the IgH locus. Considering that its expression varies during differentiation, the involvement of this factor needed to be clarified in B cells. Using a KO mouse model deleting SATB1 from the pro-B cell stage, we were able to examine the consequences of SATB1 deletion in naive and activated B cell subsets. Our model indicates firstly that SATB1 is not essential for B cell development and the establishment of a broad IgH repertoire. Second, we show that this factor exhibits an ambivalent function in mature B cells, acting sequentially as a positive and negative regulator of Ig gene transcription in naive and activated cells, respectively. Third, our study indicates that the negative regulatory function of SATB1 in B cells extends to the germinal center response in which this factor limits somatic hypermutation of Ig genes. This finding suggests that SATB1 may limit the introduction of unwanted mutations into B cells.

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

Cited by 5 publications

References 128 publications

A novel SATB1 protein isoform with different biophysical properties

A novel SATB1 protein isoform with different biophysical properties

HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells

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