Modularity of CHIP/LDB transcription complexes regulates cell differentiation

Bronstein, Revital; Segal, Daniel

doi:10.4161/fly.5.3.14854

Cited by 13 publications

(17 citation statements)

References 72 publications

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“…In Caenorrhabditis elegans , for example, the sole SSBP ortholog SAM-10 coordinates with the LDB1 ortholog in a cell-autonomous fashion to regulate synaptic differentiation (16). Similarly, the expression of the Drosophila ortholog, SSDP, is a rate-limiting cofactor that regulates combinatorial transcriptional signals from CHIP (LDB1)-APTEROUS (LHX) or CHIP (LDB1)-PANNIER (GATA) complexes (17, 18). Finally, in Zebra fish, SSDPs regulate neural patterning and sensory neuronal growth in part through LDB1 stabilization (19).…”

Section: Introductionmentioning

confidence: 99%

Requirement for Ssbp2 in Hematopoietic Stem Cell Maintenance and Stress Response

Kurasawa

Wang

et al. 2014

The Journal of Immunology

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Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and differentiation are not fully understood. Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) is a candidate acute myelogenous leukemia (AML) suppressor gene located at chromosome 5q14. SSBP2 binds the transcriptional adaptor protein Lim-domain binding protein 1 (LDB1) and enhances LDB1 stability to regulate gene expression. Notably, Ldb1 is essential for HSC specification during early development and maintenance in adults. We previously reported shortened lifespan and greater susceptibility to B cell lymphomas and carcinomas in Ssbp2 −/− mice. However, whether Ssbp2 plays a regulatory role in normal HSC function and leukemogenesis is unknown. Here, we provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells (HSPCs) in vivo. We found that hematopoietic tissues were hypoplastic in Ssbp2−/− mice and the frequency of lymphoid-primed multipotent progenitor cells in bone marrow was reduced. Other significant features of these mice were delayed recovery from 5-fluorouracil treatment and diminished multilineage reconstitution in lethally irradiated bone marrow recipients. Dramatic reduction of Notch1 transcripts and increased expression of transcripts encoding the transcription factor E2a and its downstream target Cdkn1a also distinguished Ssbp2−/− HSPCs from wild-type HSPCs. Finally, a tendency towards coordinated expression of SSBP2 and the AML suppressor NOTCH1 in a subset of The Cancer Genome Atlas AML cases suggested a role for SSBP2 in AML pathogenesis. Collectively, our results uncovered a critical regulatory function for SSBP2 in HSPC gene expression and function.

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Section: Introductionmentioning

confidence: 99%

Requirement for Ssbp2 in Hematopoietic Stem Cell Maintenance and Stress Response

Kurasawa

Wang

et al. 2014

The Journal of Immunology

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“…SEUSS (SEU) encodes an Arabidopsis protein with a conserved central domain that shares sequence homology with the dimerization domain of the LIMdomain-binding transcriptional coregulators (Franks et al, 2002), which play fundamental roles in animal development (Matthews and Visvader, 2003;Bronstein et al, 2010;Bronstein and Segal, 2011). SEU is widely expressed in Arabidopsis and functions in many developmental processes, including floral organ identity specification, gynoecium, ovule and embryo development, and lateral root initiation (Franks et al, 2002;Pfluger and Zambryski, 2004;Sridhar et al, 2006; .…”

mentioning

confidence: 99%

SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR-SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root

et al. 2016

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A decade of studies on middle cortex (MC) formation in the root endodermis of Arabidopsis (Arabidopsis thaliana) have revealed a complex regulatory network that is orchestrated by several GRAS family transcription factors, including SHORT-ROOT (SHR), SCARECROW (SCR), and SCARECROW-LIKE3 (SCL3). However, how their functions are regulated remains obscure. Here we show that mutations in the SEUSS (SEU) gene led to a higher frequency of MC formation. seu mutants had strongly reduced expression of SHR, SCR, and SCL3, suggesting that SEU positively regulates these genes. Our results further indicate that SEU physically associates with upstream regulatory sequences of SHR, SCR, and SCL3; and that SEU has distinct genetic interactions with these genes in the control of MC formation, with SCL3 being epistatic to SEU. Similar to SCL3, SEU was repressed by the phytohormone GA and induced by the GA biosynthesis inhibitor paclobutrazol, suggesting that SEU acts downstream of GA signaling to regulate MC formation. Consistently, we found that SEU mediates the regulation of SCL3 by GA signaling. Together, our study identifies SEU as a new critical player that integrates GA signaling with transcriptional inputs from the SHR-SCR-SCL3 module to regulate MC formation in the Arabidopsis root.

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“…Equally important is information on the location and spacing between transcription factor binding sites. Transcriptional co‐factors or adaptor molecules such as Chip/Ldb1 hold an important role in regulating the transcription of genes by forming protein complexes containing different combinations of transcription factors (Bronstein & Segal, ; Hobert & Westphal, ). Here we introduce Chip, the only adaptor molecule for LIM‐domain containing transcription factors in Drosophila , as a novel factor regulating cardiac gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…hold an important role in regulating the transcription of genes by forming protein complexes containing different combinations of transcription factors (Bronstein & Segal, 2011;Hobert & Westphal, 2000). Here we introduce Chip, the only adaptor molecule for LIM-domain containing transcription factors in Drosophila, as a novel factor regulating cardiac gene expression.…”

Section: Transcriptional Co-factors or Adaptor Molecules Such As Chipmentioning

confidence: 99%

Chip/Ldb1 interacts with Tailup/islet1 to regulate cardiac gene expression in Drosophila

Werner¹,

Donow²,

Pandur³

2017

Genesis

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The LIM-homeodomain transcription factor Tailup (Tup) is a component of the complex cardiac transcriptional network governing specification and differentiation of cardiac cells in Drosophila. LIM-domain containing factors are known to interact with the adaptor molecule Chip/Ldb1 to form higher order protein complexes to regulate gene expression thereby determining a cell's developmental fate. However, with respect to Drosophila heart development, it has not been investigated yet, whether Chip and tup interact to regulate the generation of different cardiac cell types. Here we show that Chip is required for normal heart development and that it interacts with tup in this context. Particularly the number of Odd skipped-expressing pericardial cells depends on balanced amounts of Chip and Tup. Data from luciferase assays using Hand- and even-skipped reporter constructs in Drosophila S2 cells indicate that Chip and Tup act as a tetrameric complex on the regulatory regions of Hand and even-skipped (eve). Finally we have identified and verified five Tup binding sites in the eve mesodermal enhancer, which adds Tup as novel factor to directly regulate eve expression. Taken together this study provides novel findings regarding cardiac gene expression regulation in Drosophila.

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Modularity of CHIP/LDB transcription complexes regulates cell differentiation

Cited by 13 publications

References 72 publications

Requirement for Ssbp2 in Hematopoietic Stem Cell Maintenance and Stress Response

Requirement for Ssbp2 in Hematopoietic Stem Cell Maintenance and Stress Response

SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR-SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root

Chip/Ldb1 interacts with Tailup/islet1 to regulate cardiac gene expression in Drosophila

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