Enhancer long-range contacts: The multi-adaptor protein LDB1 is the tie that binds

Liu, Guoyou; Dean, Ann

doi:10.1016/j.bbagrm.2019.04.003

Cited by 28 publications

(27 citation statements)

References 97 publications

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“…LMO2 serves as the bridge between SCL/TAL1 and GATA1, whereas LDB1 associates with LMO2 and is capable of self‐association (dimerization) through its N‐terminus domain . This dimerization allows LDB1‐mediated long‐range DNA looping to activate transcription, as occurs, for example, in the β‐globin locus . GATA1 and the myeloid transcription factor PU.1 have been reported to physically interact in antagonizing each other's functions by displacing other protein cofactors and/or preventing DNA binding, thus influencing cell lineage commitment decisions and activation of associated transcription programs ( and references therein).…”

Section: Gata1 Functions In Erythropoiesismentioning

confidence: 99%

“…54 This dimerization allows LDB1-mediated long-range DNA looping to activate transcription, as occurs, for example, in the β-globin locus. 55,56 GATA1 and the myeloid transcription factor PU.1 have been reported to physically interact in antagonizing each other's functions by displacing other protein cofactors and/or preventing DNA binding, thus influencing cell lineage commitment decisions and activation of associated transcription programs ( 57 and references therein). GATA1 also interacts in erythroid cells with other transcription factors such as KLF1, SP1, and GFI1B, [58][59][60] as well as with chromatin remodeling factors such as ACF/ WCRF, 48 BRG1 61 and pRB/E2F.…”

Section: Gata1 Functions In Erythropoiesismentioning

confidence: 99%

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Regulation of GATA1 levels in erythropoiesis

et al. 2019

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GATA1 is considered as the "master" transcription factor in erythropoiesis. It regulates at the transcriptional level all aspects of erythroid maturation and function, as revealed by gene knockout studies in mice and by genome-wide occupancies in erythroid cells. The GATA1 protein contains two zinc finger domains and an N-terminal transactivation domain. GATA1 translation results in the production of the full-length protein and of a shorter variant (GATA1s) lacking the N-terminal transactivation domain, which is functionally deficient in supporting erythropoiesis. GATA1 protein abundance is highly regulated in erythroid cells at different levels, including transcription, mRNA translation, posttranslational modifications, and protein degradation, in a differentiationstage-specific manner. Maintaining high GATA1 protein levels is essential in the early stages of erythroid maturation, whereas downregulating GATA1 protein levels is a necessary step in terminal erythroid differentiation. The importance of maintaining proper GATA1 protein homeostasis in erythropoiesis is demonstrated by the fact that both GATA1 loss and its overexpression result in lethal anemia. Importantly, alterations in any of those GATA1 regulatory checkpoints have been recognized as an important cause of hematological disorders such as dyserythropoiesis (with or without thrombocytopenia), β-thalassemia, Diamond-Blackfan anemia, myelodysplasia, or leukemia. In this review, we provide an overview of the multilevel regulation of GATA1 protein homeostasis in erythropoiesis and of its deregulation in hematological disease. K E Y W O R D S

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Section: Gata1 Functions In Erythropoiesismentioning

confidence: 99%

Section: Gata1 Functions In Erythropoiesismentioning

confidence: 99%

Regulation of GATA1 levels in erythropoiesis

et al. 2019

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“…Interestingly, YY1 contains 3 C2H2 domains at the C-terminus that are involved at the same time in oligomerization and DNA binding 55 . Another protein, LDB1, the Lim domain binding 1 protein, contains a dimerization domain that plays an important role in enhancer-promoter interactions in various developmental pathways [56][57][58] .…”

Section: Discussionmentioning

confidence: 99%

N-terminal domain of the architectural protein CTCF has similar structural organization and ability to self-association in bilaterian organisms

Bonchuk

Kamalyan

Mariasina

et al. 2020

Sci Rep

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ctcf is the main architectural protein found in most of the examined bilaterian organisms. the cluster of the C2H2 zinc-finger domains involved in recognition of long DNA-binding motif is only part of the protein that is evolutionarily conserved, while the N-terminal domain (NTD) has different sequences. Here, we performed biophysical characterization of CTCF NTDs from various species representing all major phylogenetic clades of higher metazoans. With the exception of Drosophilides, the N-terminal domains of CTCFs show an unstructured organization and absence of folded regions in vitro. In contrast, NTDs of Drosophila melanogaster and virilis ctcfs contain unstructured folded regions that form tetramers and dimers correspondingly in vitro. Unexpectedly, most NTDs are able to self-associate in the yeast two-hybrid and co-immunoprecipitation assays. These results suggest that NTDs of CTCFs might contribute to the organization of ctcf-mediated long-distance interactions and chromosomal architecture. Chromosomes in the genomes of all higher eukaryotes have a highly organized architecture and consist of discrete topologically associated domains (TADs) 1-5. TADs often also include smaller domains (sub-TADs) that are flanked by short boundary elements or longer regions (inter-TADs) that contain active chromatin and housekeeping genes. In addition, promoters, enhancers, silencers and insulators form a network of specific distance interactions that properly regulate gene transcription 6-9. Until now, the unresolved question remains how specific distance interactions between remote regulatory elements are established and maintained through the cell cycle 10. Currently, the best-characterized protein involved in the organization of chromosome architecture is CTCF, which was initially found as a transcriptional repressor 11. It is believed that CTCF is the main architectural protein in mammals, which is responsible for the organization of TAD boundaries and distance interactions between enhancers and promoters 12-16. CTCF was found in most of the higher eukaryotes including all studied bilateral organisms but is absent in yeast and plants 17,18. Usually CTCFs from different organisms contain the cluster of eleven C2H2 zinc-finger domains (ZF) localized in the central part of the protein. In human CTCF, ZFs from 3 to 7 recognize specific 15 bp consensus 19. The DNA-binding ZFs are the most evolutionary conserved among CTCFs that bind to similar sites in most higher eukaryotic genomes 20. Moreover, it was found that even several chromatin domains controlled by CTCF are conserved in distant species 21. Other ZF domains are usually less conserved

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“…The glutamine (Q)-rich SEUSS (SEU) protein contains a conserved domain, which shares high sequence similarity with the dimerization domain of the LIM-domain-binding (LDB) transcriptional co-regulator proteins in animals (Franks et al, 2002). The animal LDB proteins, such as LDB1 in mouse and Chip in Drosophila, play fundamental roles in the transcriptional regulation of cell-fate determination in versatile developmental processes (Agulnick et al, 1996;Morcillo et al, 1997;Matthews & Visvader, 2003;van Meyel et al, 2003;Bronstein et al, 2010;Bronstein & Segal, 2011;Love et al, 2014;Liu & Dean, 2019). Similar to its animal counterparts, SEU associates with cis-regulatory elements through its interaction with specific transcription factors to regulate gene expression during multiple developmental processes (Franks et al, 2002;Pfluger & Zambryski, 2004;Sridhar et al, 2004Sridhar et al, , 2006Grigorova et al, 2011;Gong et al, 2016;Huai et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

SEUSS integrates transcriptional and epigenetic control of root stem cell organizer specification

et al. 2020

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Proper regulation of homeotic gene expression is critical for stem cell fate in both plants and animals. In Arabidopsis thaliana, the WUSCHEL (WUS)-RELATED HOMEOBOX 5 (WOX5) gene is specifically expressed in a group of root stem cell organizer cells called the quiescent center (QC) and plays a central role in QC specification. Here, we report that the SEUSS (SEU) protein, homologous to the animal LIM-domain binding (LDB) proteins, assembles a functional transcriptional complex that regulates WOX5 expression and QC specification. SEU is physically recruited to the WOX5 promoter by the master transcription factor SCARECROW. Subsequently, SEU physically recruits the SET domain methyltransferase SDG4 to the WOX5 promoter, thus activating WOX5 expression. Thus, analogous to its animal counterparts, SEU acts as a multi-adaptor protein that integrates the actions of genetic and epigenetic regulators into a concerted transcriptional program to control root stem cell organizer specification.

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Enhancer long-range contacts: The multi-adaptor protein LDB1 is the tie that binds

Cited by 28 publications

References 97 publications

Regulation of GATA1 levels in erythropoiesis

Regulation of GATA1 levels in erythropoiesis

N-terminal domain of the architectural protein CTCF has similar structural organization and ability to self-association in bilaterian organisms

SEUSS integrates transcriptional and epigenetic control of root stem cell organizer specification

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