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Article ; Online: CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression.

Noviello, Gemma / Gjaltema, Rutger A F / Schulz, Edda G

2023 Volume 14, Issue 1, Page(s) 3225

Abstract: Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires tools to ... ...

Abstract	Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires tools to quantitatively modulate protein abundance. Here we present CasTuner, a CRISPR-based toolkit for analog tuning of endogenous gene expression. The system exploits Cas-derived repressors that are quantitatively tuned by ligand titration through a FKBP12
MeSH term(s)	Mice ; Humans ; Animals ; CRISPR-Cas Systems/genetics ; Transcription Factors/metabolism ; Genes, Homeobox ; Gene Expression
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-06-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38909-4
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Article ; Online: CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression

Gemma Noviello / Rutger A. F. Gjaltema / Edda G. Schulz

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 17

Abstract: Abstract Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires ... ...

Abstract	Abstract Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires tools to quantitatively modulate protein abundance. Here we present CasTuner, a CRISPR-based toolkit for analog tuning of endogenous gene expression. The system exploits Cas-derived repressors that are quantitatively tuned by ligand titration through a FKBP12F36V degron domain. CasTuner can be applied at the transcriptional or post-transcriptional level using a histone deacetylase (hHDAC4) fused to dCas9, or the RNA-targeting CasRx, respectively. We demonstrate analog tuning of gene expression homogeneously across cells in mouse and human cells, as opposed to KRAB-dependent CRISPR-interference systems, which exhibit digital repression. Finally, we quantify the system’s dynamics and use it to measure dose-response relationships of NANOG and OCT4 with their target genes and with the cellular phenotype. CasTuner thus provides an easy-to-implement tool to study dose-responsive processes in their physiological context.
Keywords	Science ; Q
Subject code	612 ; 570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Advances of epigenetic editing.

Gjaltema, Rutger A F / Rots, Marianne G

Current opinion in chemical biology

2020 Volume 57, Page(s) 75–81

Abstract: Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced ... ...

Abstract	Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced short palindromic repeat-dCas9 greatly accelerated the advancement of epigenetic editing, yielding preclinical therapeutic successes using a variety of epigenetic enzymes. Here, we review the current applications of these epigenetic editing tools in mammals and shed light on biochemical improvements that facilitate versatile applications.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics/methods ; Gene Editing/methods ; Genome ; Histone Code ; Humans
Language	English
Publishing date	2020-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2020.04.020
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Article ; Online: CRISPR/dCas9 Switch Systems for Temporal Transcriptional Control.

Gjaltema, Rutger A F / Schulz, Edda G

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1767, Page(s) 167–185

Abstract: In a swift revolution, CRISPR/Cas9 has reshaped the means and ease of interrogating biological questions. Particularly, mutants that result in a nuclease-deactivated Cas9 (dCas9) provide scientists with tools to modulate transcription of genomic loci at ... ...

Abstract	In a swift revolution, CRISPR/Cas9 has reshaped the means and ease of interrogating biological questions. Particularly, mutants that result in a nuclease-deactivated Cas9 (dCas9) provide scientists with tools to modulate transcription of genomic loci at will by targeting transcriptional effector domains. To interrogate the temporal order of events during transcriptional regulation, rapidly inducible CRISPR/dCas9 systems provide previously unmet molecular tools. In only a few years of time, numerous light and chemical-inducible switches have been applied to CRISPR/dCas9 to generate dCas9 switches. As these inducible switch systems are able to modulate dCas9 directly at the protein level, they rapidly affect dCas9 stability, activity, or target binding and subsequently rapidly influence downstream transcriptional events. Here we review the current state of such biotechnological CRISPR/dCas9 enhancements. Specifically we provide details on their flaws and strengths and on the differences in molecular design between the switch systems. With this we aim to provide a selection guide for researchers with keen interest in rapid temporal control over transcriptional modulation through the CRISPR/dCas9 system.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Gene Editing/methods ; Humans ; Inteins ; Models, Molecular ; RNA, Guide, CRISPR-Cas Systems/genetics ; Transcription, Genetic ; Transcriptional Activation
Chemical Substances	RNA, Guide, CRISPR-Cas Systems
Language	English
Publishing date	2018-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7774-1_8
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Article ; Online: Reciprocal regulation of endothelial-mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease.

Vanchin, Byambasuren / Sol, Marloes / Gjaltema, Rutger A F / Brinker, Marja / Kiers, Bianca / Pereira, Alexandre C / Harmsen, Martin C / Moonen, Jan-Renier A J / Krenning, Guido

Scientific reports

2021 Volume 11, Issue 1, Page(s) 17764

Abstract: Endothelial-mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. ... ...

Abstract	Endothelial-mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFβ1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.
MeSH term(s)	3' Untranslated Regions/genetics ; Cell Transdifferentiation/physiology ; Coronary Artery Disease/enzymology ; Coronary Artery Disease/pathology ; Coronary Stenosis/enzymology ; Coronary Stenosis/pathology ; Dual Specificity Phosphatase 1/biosynthesis ; Dual Specificity Phosphatase 1/genetics ; Dual Specificity Phosphatase 6/biosynthesis ; Dual Specificity Phosphatase 6/genetics ; Endothelium, Vascular/enzymology ; Endothelium, Vascular/pathology ; Enhancer of Zeste Homolog 2 Protein/physiology ; Enzyme Activation ; Gene Expression Regulation ; Genes, Reporter ; Histone Code ; Human Umbilical Vein Endothelial Cells ; Humans ; Hyperplasia ; Mesoderm/enzymology ; Mesoderm/pathology ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; Mitogen-Activated Protein Kinase 7/physiology ; Signal Transduction/physiology ; Tunica Intima/pathology ; Tunica Media/pathology
Chemical Substances	3' Untranslated Regions ; MIRN101 microRNA, human ; MIRN141 microRNA, human ; MIRN200 microRNA, human ; MicroRNAs ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; MAPK7 protein, human (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 7 (EC 2.7.11.24) ; DUSP1 protein, human (EC 3.1.3.48) ; DUSP6 protein, human (EC 3.1.3.48) ; Dual Specificity Phosphatase 1 (EC 3.1.3.48) ; Dual Specificity Phosphatase 6 (EC 3.1.3.48)
Language	English
Publishing date	2021-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-97127-4
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Article ; Online: Reciprocal regulation of endothelial–mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease

Byambasuren Vanchin / Marloes Sol / Rutger A. F. Gjaltema / Marja Brinker / Bianca Kiers / Alexandre C. Pereira / Martin C. Harmsen / Jan-Renier A. J. Moonen / Guido Krenning

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 16

Abstract: Abstract Endothelial–mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and ... ...

Abstract	Abstract Endothelial–mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFβ1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular insights into prolyl and lysyl hydroxylation of fibrillar collagens in health and disease.

Gjaltema, Rutger A F / Bank, Ruud A

Critical reviews in biochemistry and molecular biology

2017 Volume 52, Issue 1, Page(s) 74–95

Abstract: Collagen is a macromolecule that has versatile roles in physiology, ranging from structural support to mediating cell signaling. Formation of mature collagen fibrils out of procollagen α-chains requires a variety of enzymes and chaperones in a complex ... ...

Abstract	Collagen is a macromolecule that has versatile roles in physiology, ranging from structural support to mediating cell signaling. Formation of mature collagen fibrils out of procollagen α-chains requires a variety of enzymes and chaperones in a complex process spanning both intracellular and extracellular post-translational modifications. These processes include modifications of amino acids, folding of procollagen α-chains into a triple-helical configuration and subsequent stabilization, facilitation of transportation out of the cell, cleavage of propeptides, aggregation, cross-link formation, and finally the formation of mature fibrils. Disruption of any of the proteins involved in these biosynthesis steps potentially result in a variety of connective tissue diseases because of a destabilized extracellular matrix. In this review, we give a revised overview of the enzymes and chaperones currently known to be relevant to the conversion of lysine and proline into hydroxyproline and hydroxylysine, respectively, and the O-glycosylation of hydroxylysine and give insights into the consequences when these steps are disrupted.
MeSH term(s)	Animals ; Arthrogryposis/metabolism ; Arthrogryposis/pathology ; Connective Tissue Diseases/metabolism ; Connective Tissue Diseases/pathology ; Ehlers-Danlos Syndrome/metabolism ; Ehlers-Danlos Syndrome/pathology ; Fibrillar Collagens/analysis ; Fibrillar Collagens/metabolism ; Glycosylation ; Humans ; Hydroxylation ; Hydroxylysine/analysis ; Hydroxylysine/metabolism ; Hydroxyproline/analysis ; Hydroxyproline/metabolism ; Lysine/analysis ; Lysine/metabolism ; Osteogenesis Imperfecta/metabolism ; Osteogenesis Imperfecta/pathology ; Proline/analysis ; Proline/metabolism ; Protein Folding
Chemical Substances	Fibrillar Collagens ; Hydroxylysine (2GQB349IUB) ; Proline (9DLQ4CIU6V) ; Lysine (K3Z4F929H6) ; Hydroxyproline (RMB44WO89X)
Language	English
Publishing date	2017-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1000977-2
ISSN	1549-7798 ; 1381-3455 ; 1040-9238
ISSN (online)	1549-7798
ISSN	1381-3455 ; 1040-9238
DOI	10.1080/10409238.2016.1269716
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Zs.A 1024: Show issues

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Article: Distal and proximal cis-regulatory elements sense X chromosome dosage and developmental state at the Xist locus

Gjaltema, Rutger A.F. / Schwämmle, Till / Kautz, Pauline / Robson, Michael / Schöpflin, Robert / Ravid Lustig, Liat / Brandenburg, Lennart / Dunkel, Ilona / Vechiatto, Carolina / Ntini, Evgenia / Mutzel, Verena / Schmiedel, Vera / Marsico, Annalisa / Mundlos, Stefan / Schulz, Edda G.

Molecular cell. 2022 Jan. 06, v. 82, no. 1

2022

Abstract: Developmental genes such as Xist, which initiates X chromosome inactivation, are controlled by complex cis-regulatory landscapes, which decode multiple signals to establish specific spatiotemporal expression patterns. Xist integrates information on X ... ...

Abstract	Developmental genes such as Xist, which initiates X chromosome inactivation, are controlled by complex cis-regulatory landscapes, which decode multiple signals to establish specific spatiotemporal expression patterns. Xist integrates information on X chromosome dosage and developmental stage to trigger X inactivation in the epiblast specifically in female embryos. Through a pooled CRISPR screen in differentiating mouse embryonic stem cells, we identify functional enhancer elements of Xist at the onset of random X inactivation. Chromatin profiling reveals that X-dosage controls the promoter-proximal region, while differentiation cues activate several distal enhancers. The strongest distal element lies in an enhancer cluster associated with a previously unannotated Xist-enhancing regulatory transcript, which we named Xert. Developmental cues and X-dosage are thus decoded by distinct regulatory regions, which cooperate to ensure female-specific Xist upregulation at the correct developmental time. With this study, we start to disentangle how multiple, functionally distinct regulatory elements interact to generate complex expression patterns in mammals.
Keywords	chromatin ; embryonic germ layers ; females ; loci ; mice
Language	English
Dates of publication	2022-0106
Size	p. 190-208.e17.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2021.11.023
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Enhancer of zeste homolog-2 (EZH2) methyltransferase regulates transgelin/smooth muscle-22α expression in endothelial cells in response to interleukin-1β and transforming growth factor-β2.

Maleszewska, Monika / Gjaltema, Rutger A F / Krenning, Guido / Harmsen, Martin C

Cellular signalling

2015 Volume 27, Issue 8, Page(s) 1589–1596

Abstract: ... including myofibroblasts and smooth muscle cells. It is an F-actin binding protein that regulates ...

Abstract	Smooth muscle-22α (SM22α), encoded by transgelin (TAGLN), is expressed in mesenchymal lineage cells, including myofibroblasts and smooth muscle cells. It is an F-actin binding protein that regulates the organization of actin cytoskeleton, cellular contractility and motility. SM22α is crucial for the maintenance of smooth muscle cell phenotype and its function. SM22α is also expressed in the processes of mesenchymal transition of epithelial (EMT) or endothelial cells (EndMT). The expression of TAGLN/SM22α is induced by transforming growth factor-β (TGFβ) signaling and enhanced by concomitant interleukin-1β (IL-1β) signaling. We investigated the epigenetic regulation of TAGLN expression by enhancer of zeste homolog-2 (EZH2), the methyltransferase of Polycomb, in the context of TGFβ and IL-1β signaling in endothelial cells. We demonstrate that the expression of EZH2 in endothelial cells was regulated by the inflammatory cytokine IL-1β. A decrease in both expression and activity of EZH2 led to an increase in TAGLN expression. Inhibition of EZH2 augmented TGFβ2-induced SM22α expression. The decrease of EZH2 levels in endothelial cells co-stimulated with IL-1β and TGFβ2 correlated with decreased H3K27me3 levels at the TAGLN proximal promoter. Moreover, the SM22α expression increased. Taken together, this suggests that EZH2 regulates the chromatin structure at the TAGLN promoter through tri-methylation of H3K27. EZH2 therefore acts as an epigenetic integrator of IL-1β and TGFβ2 signaling, providing an example of how cellular signaling can be resolved at the level of epigenetic regulation. Since IL-1β and TGFβ2 represent the pro-inflammatory and pro-fibrotic conditions during vascular fibroproliferative disease, we surmise that EZH2, as the molecule that integrates their signaling, could also be a promising target for development of future therapy.
MeSH term(s)	Cell Line, Transformed ; Chromatin Assembly and Disassembly/drug effects ; DNA Methylation/drug effects ; Enhancer of Zeste Homolog 2 Protein ; Enzyme Inhibitors/pharmacology ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation ; Histones/metabolism ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/enzymology ; Humans ; Interleukin-1beta/pharmacology ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Muscle Proteins/genetics ; Muscle Proteins/metabolism ; Polycomb Repressive Complex 2/antagonists & inhibitors ; Polycomb Repressive Complex 2/genetics ; Polycomb Repressive Complex 2/metabolism ; Promoter Regions, Genetic ; RNA Interference ; Signal Transduction/drug effects ; Transfection ; Transforming Growth Factor beta2/pharmacology ; Vascular Remodeling
Chemical Substances	Enzyme Inhibitors ; Histones ; Interleukin-1beta ; Microfilament Proteins ; Muscle Proteins ; Transforming Growth Factor beta2 ; transgelin ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2015-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2015.04.008
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Article ; Online: Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2.

Gjaltema, Rutger A F / van der Stoel, Miesje M / Boersema, Miriam / Bank, Ruud A

Proceedings of the National Academy of Sciences of the United States of America

2016 Volume 113, Issue 26, Page(s) 7142–7147

Abstract: Collagens are subjected to extensive posttranslational modifications, such as lysine hydroxylation. Bruck syndrome (BS) is a connective tissue disorder characterized at the molecular level by a loss of telopeptide lysine hydroxylation, resulting in ... ...

Abstract	Collagens are subjected to extensive posttranslational modifications, such as lysine hydroxylation. Bruck syndrome (BS) is a connective tissue disorder characterized at the molecular level by a loss of telopeptide lysine hydroxylation, resulting in reduced collagen pyridinoline cross-linking. BS results from mutations in the genes coding for lysyl hydroxylase (LH) 2 or peptidyl-prolyl cis-trans isomerase (PPIase) FKBP65. Given that the immunophilin FKBP65 does not exhibit LH activity, it is likely that LH2 activity is somehow dependent on FKPB65. In this report, we provide insights regarding the interplay between LH2 and FKBP65. We found that FKBP65 forms complexes with LH2 splice variants LH2A and LH2B but not with LH1 and LH3. Ablating the catalytic activity of FKBP65 or LH2 did not affect complex formation. Both depletion of FKBP65 and inhibition of FKBP65 PPIase activity reduced the dimeric (active) form of LH2 but did not affect the binding of monomeric (inactive) LH2 to procollagen Iα1. Furthermore, we show that LH2A and LH2B cannot form heterodimers with each other but are able to form heterodimers with LH1 and LH3. Collectively, our results indicate that FKBP65 is linked to pyridinoline cross-linking by specifically mediating the dimerization of LH2. Moreover, FKBP65 does not interact with LH1 and LH3, explaining why in BS triple-helical hydroxylysines are not affected. Our results provide a mechanistic link between FKBP65 and the loss of pyridinolines and may hold the key to future treatments for diseases related to collagen cross-linking anomalies, such as fibrosis and cancer.
MeSH term(s)	Amino Acids/chemistry ; Amino Acids/metabolism ; Arthrogryposis/enzymology ; Arthrogryposis/genetics ; Arthrogryposis/metabolism ; Collagen/chemistry ; Collagen/genetics ; Collagen/metabolism ; Collagen Type I/chemistry ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Cross-Linking Reagents/chemistry ; Dimerization ; Humans ; Osteogenesis Imperfecta/enzymology ; Osteogenesis Imperfecta/genetics ; Osteogenesis Imperfecta/metabolism ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism ; Protein Binding ; Protein Processing, Post-Translational ; Tacrolimus Binding Proteins/genetics ; Tacrolimus Binding Proteins/metabolism
Chemical Substances	Amino Acids ; Collagen Type I ; Cross-Linking Reagents ; collagen type I, alpha 1 chain ; pyridinoline (63800-01-1) ; Collagen (9007-34-5) ; PLOD2 protein, human (EC 1.14.11.4) ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase (EC 1.14.11.4) ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; FKBP10 protein, human (EC 5.2.1.8)
Language	English
Publishing date	2016--28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1600074113
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