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Article ; Online: Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure.

Simonson, Bridget / Chaffin, Mark / Hill, Matthew C / Atwa, Ondine / Guedira, Yasmine / Bhasin, Harshit / Hall, Amelia W / Hayat, Sikander / Baumgart, Simon / Bedi, Kenneth C / Margulies, Kenneth B / Klattenhoff, Carla A / Ellinor, Patrick T

Cell reports

2023 Volume 42, Issue 2, Page(s) 112086

Abstract: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile ... ...

Abstract	Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile the transcriptomes of over 99,000 human cardiac nuclei from the non-infarct region of the left ventricle of 7 ICM transplant recipients and 8 non-failing (NF) controls. We find the cellular composition of the ischemic heart is significantly altered, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in patients with ICM. We show that there is increased LAMININ signaling from endothelial cells to other cell types in ICM compared with NF. Finally, we find that the transcriptional changes that occur in ICM are similar to those in hypertrophic and dilated cardiomyopathies and that the mining of these combined datasets can identify druggable genes that could be used to target end-stage heart failure.
MeSH term(s)	Humans ; Endothelial Cells/metabolism ; Myocardial Ischemia/genetics ; Myocardial Ischemia/metabolism ; Heart Failure/genetics ; Heart Failure/metabolism ; Cardiomyopathy, Dilated ; Sequence Analysis, RNA ; Cardiomyopathies/genetics
Language	English
Publishing date	2023-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112086
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Transcriptional profile of the rat cardiovascular system at single cell resolution.

Arduini, Alessandro / Fleming, Stephen J / Xiao, Ling / Hall, Amelia W / Akkad, Amer-Denis / Chaffin, Mark / Bendinelli, Kayla J / Tucker, Nathan R / Papangeli, Irinna / Mantineo, Helene / Babadi, Mehrtash / Stegmann, Christian M / García-Cardeña, Guillermo / Lindsay, Mark E / Klattenhoff, Carla / Ellinor, Patrick T

bioRxiv : the preprint server for biology

2023

Abstract: Background: Despite the critical role of the cardiovascular system, our understanding of its cellular and transcriptional diversity remains limited. We therefore sought to characterize the cellular composition, phenotypes, molecular pathways, and ... ...

Abstract	Background: Despite the critical role of the cardiovascular system, our understanding of its cellular and transcriptional diversity remains limited. We therefore sought to characterize the cellular composition, phenotypes, molecular pathways, and communication networks between cell types at the tissue and sub-tissue level across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We obtained high quality tissue samples under controlled conditions that reveal a level of cellular detail so far inaccessible in human studies. Methods and results: We performed single nucleus RNA-sequencing in 78 samples in 10 distinct regions including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins (PV), which produced an aggregate map of 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, including a number of rare cell types such as PV cardiomyocytes and non-myelinating Schwann cells (NMSCs), and unique groups of vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and fibroblasts (FBs), which gave rise to a detailed cell type distribution across tissues. We demonstrated differences in the cellular composition across different cardiac regions and tissue-specific differences in transcription for each cell type, highlighting the molecular diversity and complex tissue architecture of the cardiovascular system. Specifically, we observed great transcriptional heterogeneities among ECs and FBs. Importantly, several cell subtypes had a unique regional localization such as a subtype of VSMCs enriched in the large vasculature. We found the cellular makeup of PV tissue is closer to heart tissue than to the large arteries. We further explored the ligand-receptor repertoire across cell clusters and tissues, and observed tissue-enriched cellular communication networks, including heightened Conclusions: Through a large single nucleus sequencing effort encompassing over 500,000 nuclei, we broadened our understanding of cellular transcription in the healthy cardiovascular system. The existence of tissue-restricted cellular phenotypes suggests regional regulation of cardiovascular physiology. The overall conservation in gene expression and molecular pathways across rat and human cell types, together with our detailed transcriptional characterization of each cell type, offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease.
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.14.567085
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Article ; Online: Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure

Bridget Simonson / Mark Chaffin / Matthew C. Hill / Ondine Atwa / Yasmine Guedira / Harshit Bhasin / Amelia W. Hall / Sikander Hayat / Simon Baumgart / Kenneth C. Bedi, Jr. / Kenneth B. Margulies / Carla A. Klattenhoff / Patrick T. Ellinor

Cell Reports, Vol 42, Iss 2, Pp 112086- (2023)

2023

Abstract: Summary: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we ...

Abstract	Summary: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile the transcriptomes of over 99,000 human cardiac nuclei from the non-infarct region of the left ventricle of 7 ICM transplant recipients and 8 non-failing (NF) controls. We find the cellular composition of the ischemic heart is significantly altered, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in patients with ICM. We show that there is increased LAMININ signaling from endothelial cells to other cell types in ICM compared with NF. Finally, we find that the transcriptional changes that occur in ICM are similar to those in hypertrophic and dilated cardiomyopathies and that the mining of these combined datasets can identify druggable genes that could be used to target end-stage heart failure.
Keywords	CP: Molecular biology ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Aortic Cellular Diversity and Quantitative Genome-Wide Association Study Trait Prioritization Through Single-Nuclear RNA Sequencing of the Aneurysmal Human Aorta.

Chou, Elizabeth L / Chaffin, Mark / Simonson, Bridget / Pirruccello, James P / Akkad, Amer-Denis / Nekoui, Mahan / Lino Cardenas, Christian Lacks / Bedi, Kenneth C / Nash, Craig / Juric, Dejan / Stone, James R / Isselbacher, Eric M / Margulies, Kenneth B / Klattenhoff, Carla / Ellinor, Patrick T / Lindsay, Mark E

Arteriosclerosis, thrombosis, and vascular biology

2022 Volume 42, Issue 11, Page(s) 1355–1374

Abstract: Background: Mural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue.: ... ...

Abstract	Background: Mural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue. Methods: Single-nuclear RNA sequencing was performed on 13 samples from human donors, 6 with thoracic aortic aneurysm, and 7 without aneurysm. Individual transcriptomes were then clustered based on transcriptional profiles. Clusters were used for between-disease differential gene expression analyses, subcluster analysis, and analyzed for intersection with genetic aortic trait data. Results: We sequenced 71 689 nuclei from human thoracic aortas and identified 14 clusters, aligning with 11 cell types, predominantly vascular smooth muscle cells (VSMCs) consistent with aortic histology. With unbiased methodology, we found 7 vascular smooth muscle cell and 6 fibroblast subclusters. Differentially expressed genes analysis revealed a vascular smooth muscle cell group accounting for the majority of differential gene expression. Fibroblast populations in aneurysm exhibit distinct behavior with almost complete disappearance of quiescent fibroblasts. Differentially expressed genes were used to prioritize genes at aortic diameter and distensibility genome-wide association study loci highlighting the genes Conclusions: Using nuclear RNA sequencing, we describe the cellular diversity of healthy and aneurysmal human ascending aorta. Sporadic aortic aneurysm is characterized by differential gene expression within known cellular classes rather than by the appearance of novel cellular forms. Single-nuclear RNA sequencing of aortic tissue can be used to prioritize genes at aortic trait loci.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Muscle, Smooth, Vascular/metabolism ; Actinin/genetics ; RNA, Nuclear/metabolism ; Aorta/pathology ; Myocytes, Smooth Muscle/metabolism ; Aortic Aneurysm, Thoracic/pathology ; Aortic Aneurysm/metabolism ; Sequence Analysis, RNA ; Transforming Growth Factor beta/metabolism
Chemical Substances	Actinin (11003-00-2) ; RNA, Nuclear ; Transforming Growth Factor beta
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.122.317953
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Article: Biogenesis and germline functions of piRNAs.

Klattenhoff, Carla / Theurkauf, William

Development (Cambridge, England)

2008 Volume 135, Issue 1, Page(s) 3–9

Abstract: Small interfering RNAs and microRNAs are generated from double-stranded RNA precursors by the Dicer endonucleases, and function with Argonaute-family proteins to target transcript destruction or to silence translation. A distinct class of 24- to 30- ... ...

Abstract	Small interfering RNAs and microRNAs are generated from double-stranded RNA precursors by the Dicer endonucleases, and function with Argonaute-family proteins to target transcript destruction or to silence translation. A distinct class of 24- to 30-nucleotide-long RNAs, produced by a Dicer-independent mechanism, associates with Piwi-class Argonaute proteins. Studies in flies, fish and mice implicate these Piwi-associated RNAs (piRNAs) in germline development, silencing of selfish DNA elements, and in maintaining germline DNA integrity. However, whether piRNAs primarily control chromatin organization, gene transcription, RNA stability or RNA translation is not well understood, neither is piRNA biogenesis. Here, we review recent studies of piRNA production and function, and discuss unanswered questions about this intriguing new class of small RNAs.
MeSH term(s)	Animals ; Fertility ; Germ Cells/metabolism ; RNA, Small Interfering/biosynthesis ; RNA, Small Interfering/genetics ; Sex Determination Processes ; Stem Cells/cytology
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.006486
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Article ; Online: Screening for novel regulators of embryonic stem cell identity.

Subramanian, Vidya / Klattenhoff, Carla A / Boyer, Laurie A

Cell stem cell

2009 Volume 4, Issue 5, Page(s) 377–378

Abstract: Two recent studies, including one in this issue of Cell Stem Cell, have identified novel regulators of embryonic stem cell (ESC) self-renewal using genome-wide RNAi screens in mouse ESCs (Ding et al., 2009; Hu et al., 2009) and have further expanded the ... ...

Abstract	Two recent studies, including one in this issue of Cell Stem Cell, have identified novel regulators of embryonic stem cell (ESC) self-renewal using genome-wide RNAi screens in mouse ESCs (Ding et al., 2009; Hu et al., 2009) and have further expanded the repertoire of factors that regulate ESC identity.
MeSH term(s)	Animals ; Cell Differentiation ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Gene Expression Profiling ; Genome ; Mice ; RNA, Small Interfering/metabolism ; Transcription Factors/metabolism
Chemical Substances	RNA, Small Interfering ; Transcription Factors
Language	English
Publishing date	2009-05-08
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2009.04.006
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Article: Cholesterol depletion induces PKA-mediated basolateral-to-apical transcytosis of the scavenger receptor class B type I in MDCK cells.

Burgos, Patricia V / Klattenhoff, Carla / de la Fuente, Erwin / Rigotti, Attilio / González, Alfonso

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

2004 Volume 101, Issue 11, Page(s) 3845–3850

Abstract: Cholesterol-based membrane microdomains, or lipid rafts, are believed to play important, yet poorly defined, roles in protein trafficking and signal transduction. In polarized epithelial cells, the current view is that rafts are involved in apical but ... ...

Abstract	Cholesterol-based membrane microdomains, or lipid rafts, are believed to play important, yet poorly defined, roles in protein trafficking and signal transduction. In polarized epithelial cells, the current view is that rafts are involved in apical but not in basolateral protein transport from the trans-Golgi network (TGN). We report here that cholesterol is required in a post-TGN mechanism of basolateral regionalization. Permanently transfected Madin-Darby canine kidney cells segregated the caveolae/raft-associated high-density lipoprotein scavenger receptor class B type I (SR-BI) predominantly to the basolateral domain where it was constitutively internalized and recycled basolaterally. Acute cholesterol depletion did not significantly alter SR-BI internalization, implying a cholesterol depletion-insensitive endocytic process but instead induced its transcytosis through a protein kinase A (PKA)- and microtubule-dependent mechanism. Forskolin also elicited SR-BI transcytosis. The basolateral distribution of endogenous epidermal growth factor receptor remained unaffected. Strikingly, cholesterol depletion induced PKA activity without increasing the cAMP levels. Thus, our results are consistent with a scenario in which cholesterol-based rafts promote internalization and basolateral recycling of internalized SR-BI whereas a PKA pool sensitive to cholesterol depletion mediates SR-BI transcytosis. Regulated transcytosis of SR-BI may provide an additional mechanism to control cholesterol homeostasis. These results disclose relationships between cholesterol-based rafts and PKA activity operating in a post-TGN mechanism of regulated apical-to-basolateral cell surface protein distribution.
MeSH term(s)	Animals ; CD36 Antigens ; Cholesterol/metabolism ; Colforsin/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dogs ; Membrane Proteins ; Microtubules/metabolism ; Protein Transport/physiology ; Receptors, Immunologic/metabolism ; Receptors, Lipoprotein ; Receptors, Scavenger ; Scavenger Receptors, Class B
Chemical Substances	CD36 Antigens ; Membrane Proteins ; Receptors, Immunologic ; Receptors, Lipoprotein ; Receptors, Scavenger ; Scarb1 protein, mouse ; Scavenger Receptors, Class B ; Colforsin (1F7A44V6OU) ; Cholesterol (97C5T2UQ7J) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
Language	English
Publishing date	2004-03-16
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.0400295101
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Article ; Online: Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.

Klattenhoff, Carla A / Scheuermann, Johanna C / Surface, Lauren E / Bradley, Robert K / Fields, Paul A / Steinhauser, Matthew L / Ding, Huiming / Butty, Vincent L / Torrey, Lillian / Haas, Simon / Abo, Ryan / Tabebordbar, Mohammadsharif / Lee, Richard T / Burge, Christopher B / Boyer, Laurie A

Cell

2013 Volume 152, Issue 3, Page(s) 570–583

Abstract: Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell ...

Abstract	Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Differentiation ; Embryonic Stem Cells/metabolism ; Gene Regulatory Networks ; Humans ; Mesoderm/cytology ; Mesoderm/metabolism ; Mice ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Polycomb Repressive Complex 2/metabolism ; RNA, Long Noncoding ; Rats
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Mesp1 protein, mouse ; RNA, Long Noncoding ; Suz12 protein, mouse ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2013-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2013.01.003
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.

Klattenhoff, Carla / Bratu, Diana P / McGinnis-Schultz, Nadine / Koppetsch, Birgit S / Cook, Heather A / Theurkauf, William E

Developmental cell

2006 Volume 12, Issue 1, Page(s) 45–55

Abstract: Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule ... ...

Abstract	Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.
MeSH term(s)	Animals ; Body Patterning/genetics ; Cell Cycle Proteins/metabolism ; Checkpoint Kinase 2 ; DEAD-box RNA Helicases/metabolism ; DNA Damage ; Drosophila Proteins/metabolism ; Drosophila melanogaster/cytology ; Drosophila melanogaster/embryology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/embryology ; Embryo, Nonmammalian/metabolism ; Female ; Germ-Line Mutation ; Microtubules/metabolism ; Models, Biological ; Mutation/genetics ; Ovary/cytology ; Ovary/pathology ; Peptide Initiation Factors/metabolism ; Phosphorylation ; Protein Transport ; Protein-Serine-Threonine Kinases/metabolism ; RNA Helicases/metabolism ; RNA, Small Interfering/genetics ; Suppression, Genetic ; Transforming Growth Factor alpha/metabolism
Chemical Substances	Cell Cycle Proteins ; Drosophila Proteins ; Peptide Initiation Factors ; RNA, Small Interfering ; Transforming Growth Factor alpha ; aub protein, Drosophila ; grk protein, Drosophila ; osk protein, Drosophila ; Checkpoint Kinase 2 (EC 2.7.1.11) ; Mei-41 protein, Drosophila (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; lok protein, Drosophila (EC 2.7.11.1) ; armi protein, Drosophila (EC 2.7.7.-) ; vas protein, Drosophila (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2006-12-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2006.12.001
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Article ; Online: The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters.

Klattenhoff, Carla / Xi, Hualin / Li, Chengjian / Lee, Soohyun / Xu, Jia / Khurana, Jaspreet S / Zhang, Fan / Schultz, Nadine / Koppetsch, Birgit S / Nowosielska, Anetta / Seitz, Herve / Zamore, Phillip D / Weng, Zhiping / Theurkauf, William E

Cell

2009 Volume 138, Issue 6, Page(s) 1137–1149

Abstract: Piwi-interacting RNAs (piRNAs) silence transposons and maintain genome integrity during germline development. In Drosophila, transposon-rich heterochromatic clusters encode piRNAs either on both genomic strands (dual-strand clusters) or predominantly one ...

Abstract	Piwi-interacting RNAs (piRNAs) silence transposons and maintain genome integrity during germline development. In Drosophila, transposon-rich heterochromatic clusters encode piRNAs either on both genomic strands (dual-strand clusters) or predominantly one genomic strand (uni-strand clusters). Primary piRNAs derived from these clusters are proposed to drive a ping-pong amplification cycle catalyzed by proteins that localize to the perinuclear nuage. We show that the HP1 homolog Rhino is required for nuage organization, transposon silencing, and ping-pong amplification of piRNAs. rhi mutations virtually eliminate piRNAs from the dual-strand clusters and block production of putative precursor RNAs from both strands of the major 42AB dual-strand cluster, but not of transcripts or piRNAs from the uni-strand clusters. Furthermore, Rhino protein associates with the 42AB dual-strand cluster,but does not bind to uni-strand cluster 2 or flamenco. Rhino thus appears to promote transcription of dual-strand clusters, leading to production of piRNAs that drive the ping-pong amplification cycle.
MeSH term(s)	Animals ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Transposable Elements ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Gene Silencing ; Heterochromatin/metabolism ; RNA, Small Interfering/metabolism ; Transcription, Genetic
Chemical Substances	Chromosomal Proteins, Non-Histone ; DNA Transposable Elements ; Drosophila Proteins ; Heterochromatin ; RNA, Small Interfering ; rhi protein, Drosophila
Language	English
Publishing date	2009-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2009.07.014
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