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Article ; Online: Gastric Wall Thickness and the Choice of Linear Staples in Laparoscopic Sleeve Gastrectomy: Challenging Conventional Concepts.

Abu-Ghanem, Yasmin / Meydan, Chanan / Segev, Lior / Rubin, Moshe / Blumenfeld, Orit / Spivak, Hadar

2017 Volume 27, Issue 3, Page(s) 837–843

Abstract: Background: Little evidence is available on the choice of linear staple reloads in laparoscopic sleeve gastrectomy (LSG). Previous literature recommends matching closed staple height (CSH) to tissue-thickness (TT) to avoid ischemia. Our objective was to ...

Abstract	Background: Little evidence is available on the choice of linear staple reloads in laparoscopic sleeve gastrectomy (LSG). Previous literature recommends matching closed staple height (CSH) to tissue-thickness (TT) to avoid ischemia. Our objective was to examine feasibility and safety of "tight" hemostatic (CSH/TT <1) stapling and map the entire gastric wall TT in LSG patients. Methods: Prospectively collected outcomes on 202 consecutive patients who underwent LSG with tight order of staples (Ethicon Endosurgery) in this order: pre-pylorus-black (CSH = 2.3 mm), antrum-green (CSH = 2.0 mm), antrum/body-blue (CSH = 1.5 mm), and white (CSH = 1.0 mm) on the body and fundus. Measurements of entire gastric wall TT were made on the first 100 patients' gastric specimens with an electronic-dogmatic indicator. Results: Study included 147 females and 55 males with a mean age of 41.5 ± 11.9 years and body mass index of 41.5 ± 3.8 kg/m Conclusions: Our study suggests that reloads with CSH/TT <1 in LSG including staples with CSH of 1 mm on body and fundus are safe. The results challenge the concept that tight stapling cause's ischemia. Since tight reloads are designed to improve hemostasis, their application could have clinical benefit.
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-016-2516-2
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Article ; Online: Immediate Metabolic Response Following Sleeve Gastrectomy in Obese Diabetics.

Meydan, Chanan / Goldstein, Nir / Weiss-Shwartz, Efrat / Lederfine, Doron / Goitein, David / Rubin, Moshe / Spivak, Hadar

Obesity surgery

2015 Volume 25, Issue 11, Page(s) 2023–2029

Abstract: Background: Although laparoscopic sleeve gastrectomy (LSG) has been shown to have a long-term antidiabetic effect, little is known regarding the immediate response to surgery. This study's objective was to evaluate the glycemic and lipid metabolic ... ...

Abstract	Background: Although laparoscopic sleeve gastrectomy (LSG) has been shown to have a long-term antidiabetic effect, little is known regarding the immediate response to surgery. This study's objective was to evaluate the glycemic and lipid metabolic response in the first postoperative week. Methods: The study included 21 obese diabetic participants. Glycemic markers, lipids, and hepatic function tests were measured just prior to surgery and at 1 week and 3 months postoperatively. Two participants were dropped prior to all measurements due to technical reasons, and two more were lost to follow-up. Results: At 1 week after surgery, compared to preoperative baseline, we found reduced hemoglobin A1c (7.63 to 7.31, P < 0.001), insulin (24.96 to 10.92, P < 0.05), and borderline significant homeostatic model assessment insulin resistance (HOMA-IR, 9.48 to 3.91, P > 0.05). Low-density lipoprotein (LDL) cholesterol increased and high-density lipoprotein (HDL) cholesterol decreased. Three months after surgery, hemoglobin A1c, insulin, and HOMA-IR continued to decrease (6.05, 7.11, and 1.92, respectively, P < 0.05), with hemoglobin A1c correlated to weight loss (P < 0.05). Triglycerides, triglyceride to HDL ratio, and total cholesterol to HDL ratio also decreased, but there was no significant change in LDL cholesterol or HDL versus presurgery levels. Reduced triglyceride levels were correlated with reduced alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) (P < 0.05). Conclusions: LSG is associated with marked antidiabetic effects as early as 1 week after surgery, unrelated to weight loss. The antidiabetic effect improves at 3 months. Triglyceride reduction was associated with improved hepatic functions, but cholesterol did not show a meaningful reduction.
MeSH term(s)	Adult ; Blood Glucose/metabolism ; Cholesterol/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/surgery ; Female ; Follow-Up Studies ; Gastrectomy/methods ; Glycated Hemoglobin A/metabolism ; Humans ; Insulin/blood ; Insulin Resistance ; Lipids/blood ; Male ; Obesity, Morbid/metabolism ; Obesity, Morbid/surgery ; Postoperative Period ; Time Factors ; Triglycerides/blood
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; Insulin ; Lipids ; Triglycerides ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-015-1669-8
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Article ; Online: Detection of weakly conserved ancestral mammalian regulatory sequences by primate comparisons.

Wang, Qian-fei / Prabhakar, Shyam / Chanan, Sumita / Cheng, Jan-Fang / Rubin, Edward M / Boffelli, Dario

Genome biology

2007 Volume 8, Issue 1, Page(s) R1

Abstract: Background: Genomic comparisons between human and distant, non-primate mammals are commonly used to identify cis-regulatory elements based on constrained sequence evolution. However, these methods fail to detect functional elements that are too weakly ... ...

Abstract	Background: Genomic comparisons between human and distant, non-primate mammals are commonly used to identify cis-regulatory elements based on constrained sequence evolution. However, these methods fail to detect functional elements that are too weakly conserved among mammals to distinguish them from non-functional DNA. Results: To evaluate a strategy for large scale genome annotation that is complementary to the commonly used distal species comparisons, we explored the potential of deep intra-primate sequence comparisons. We sequenced the orthologs of 558 kb of human genomic sequence, covering multiple loci involved in cholesterol homeostasis, in 6 non-human primates. Our analysis identified six non-coding DNA elements displaying significant conservation among primates but undetectable in more distant comparisons. In vitro and in vivo tests revealed that at least three of these six elements have regulatory function. Notably, the mouse orthologs of these three functional human sequences had regulatory activity despite their lack of significant sequence conservation, indicating that they are ancestral mammalian cis-regulatory elements. These regulatory elements could be detected even in a smaller set of three primate species including human, rhesus and marmoset. Conclusion: We have demonstrated that intra-primate sequence comparisons can be used to identify functional modules in large genomic regions, including cis-regulatory elements that are not detectable through comparison with non-mammalian genomes. With the available human and rhesus genomes and that of marmoset, which is being actively sequenced, this strategy can be extended to the whole genome in the near future.
MeSH term(s)	Animals ; Base Sequence ; Conserved Sequence ; DNA, Intergenic/genetics ; Evolution, Molecular ; Genome ; Haplorhini/genetics ; Mammals/genetics ; Molecular Sequence Data ; Phylogeny ; Primates/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Sequence Homology, Nucleic Acid ; Species Specificity ; Sterol Regulatory Element Binding Protein 1/genetics
Chemical Substances	DNA, Intergenic ; Sterol Regulatory Element Binding Protein 1
Language	English
Publishing date	2007
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/gb-2007-8-1-r1
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Article: Negative regulation of receptor tyrosine kinases: unexpected links to c-Cbl and receptor ubiquitylation.

Rubin, Chanan / Gur, Gal / Yarden, Yosef

Cell research

2005 Volume 15, Issue 1, Page(s) 66–71

Abstract: Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these ...

Abstract	Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ultimately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl-mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty.
MeSH term(s)	Animals ; Down-Regulation ; Endocytosis ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; Growth Substances/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Models, Biological ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction ; Transcription, Genetic ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Growth Substances ; LRIG1 protein, human ; Membrane Glycoproteins ; Proto-Oncogene Proteins ; Ubiquitin ; Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2005-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/sj.cr.7290268
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Article: RNA Elimination Machinery Targeting Meiotic mRNAs Promotes Facultative Heterochromatin Formation

Zofall, Martin / Yamanaka, Soichiro / Reyes-Turcu, Francisca E / Zhang, Ke / Rubin, Chanan / Grewal, Shiv I. S

Science. 2012 Jan. 6, v. 335, no. 6064

2012

Abstract: Facultative heterochromatin that changes during cellular differentiation coordinates regulated gene expression, but its assembly is poorly understood. Here, we describe facultative heterochromatin islands in fission yeast and show that their formation at ...

Abstract	Facultative heterochromatin that changes during cellular differentiation coordinates regulated gene expression, but its assembly is poorly understood. Here, we describe facultative heterochromatin islands in fission yeast and show that their formation at meiotic genes requires factors that eliminate meiotic messenger RNAs (mRNAs) during vegetative growth. Blocking production of meiotic mRNA or loss of RNA elimination factors, including Mmi1 and Red1 proteins, abolishes heterochromatin islands. RNA elimination machinery is enriched at meiotic loci and interacts with Clr4/SUV39h, a methyltransferase involved in heterochromatin assembly. Heterochromatin islands disassemble in response to nutritional signals that induce sexual differentiation. This process involves the antisilencing factor Epe1, the loss of which causes dramatic increase in heterochromatic loci. Our analyses uncover unexpected regulatory roles for mRNA-processing factors that assemble dynamic heterochromatin to modulate gene expression.
Keywords	Schizosaccharomyces pombe ; cell differentiation ; gene expression ; genes ; heterochromatin ; loci ; meiosis ; messenger RNA ; methyltransferases ; sexual development ; vegetative growth
Language	English
Dates of publication	2012-0106
Size	p. 96-100.
Publishing place	American Association for the Advancement of Science
Document type	Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1211651
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Article: c-Cbl is a critical modulator of the Ron tyrosine kinase receptor.

Penengo, Lorenza / Rubin, Chanan / Yarden, Yosef / Gaudino, Giovanni

Oncogene

2003 Volume 22, Issue 24, Page(s) 3669–3679

Abstract: Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a ... ...

Abstract	Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the multifunctional docking site as well as to a juxtamembrane tyrosine autophosphorylation site. c-Cbl recruitment to these two sites results in polyubiquitylation of Ron molecules, which are subsequently sorted for endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl are found also in physical complexes that include Grb2, these associations are insufficient for productive ubiquitylation of Ron. Our results shed light on the mechanism of receptor desensitization mediated by c-Cbl and its binding partner Grb2.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Endocytosis ; GRB2 Adaptor Protein ; Humans ; Proteins/physiology ; Proto-Oncogene Proteins/chemistry ; Proto-Oncogene Proteins/physiology ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, Cell Surface/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases ; src Homology Domains
Chemical Substances	Adaptor Proteins, Signal Transducing ; GRB2 Adaptor Protein ; GRB2 protein, human ; Proteins ; Proto-Oncogene Proteins ; Receptors, Cell Surface ; Ubiquitin ; Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; RON protein (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; CBL protein, human (EC 6.3.2.-)
Language	English
Publishing date	2003-06-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/sj.onc.1206585
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Article: Phosphorylation of carboxyl-terminal tyrosines modulates the specificity of Sprouty-2 inhibition of different signaling pathways.

Rubin, Chanan / Zwang, Yaara / Vaisman, Nora / Ron, Dina / Yarden, Yosef

The Journal of biological chemistry

2005 Volume 280, Issue 10, Page(s) 9735–9744

Abstract: Sprouty proteins are evolutionarily conserved negative feedback regulators of multiple receptor tyrosine kinases. Mammalian versions of these proteins differentially regulate signaling induced by the fibroblast and the epidermal growth factors (FGF and ... ...

Abstract	Sprouty proteins are evolutionarily conserved negative feedback regulators of multiple receptor tyrosine kinases. Mammalian versions of these proteins differentially regulate signaling induced by the fibroblast and the epidermal growth factors (FGF and EGF, respectively). Herein we show that, although both growth factors elevate expression of Sprouty-2, FGF- and not EGF-induced activation of the Erk/MAPK pathway is inhibited by Sprouty-2. Attenuation of FGF-signaling is accompanied by the induction of Sprouty-2 phosphorylation on the amino-terminal as well as carboxyl-terminal tyrosine residues, which are less effectively modified upon EGF treatment. Mutagenesis of carboxyl-terminal tyrosines, especially a newly identified phosphorylation site, tyrosine 227, impaired the inhibitory activity of Sprouty-2. These results attribute a novel role for carboxyl-terminal tyrosine residues and yet unidentified phosphotyrosine-binding proteins in the differential regulation of Sprouty-2 activity.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; CHO Cells ; COS Cells ; Cell Line ; Chlorocebus aethiops ; Cricetinae ; Cysteine ; GRB2 Adaptor Protein ; Humans ; MAP Kinase Signaling System/physiology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Binding ; RNA Interference ; Rats ; Recombinant Proteins/metabolism ; Signal Transduction/physiology ; Transfection
Chemical Substances	Adaptor Proteins, Signal Transducing ; GRB2 Adaptor Protein ; GRB2 protein, human ; Grb2 protein, rat ; Nerve Tissue Proteins ; Recombinant Proteins ; Spry2 protein, rat ; Phosphotyrosine (21820-51-9) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2005-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M408308200
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Article ; Online: RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation.

Zofall, Martin / Yamanaka, Soichiro / Reyes-Turcu, Francisca E / Zhang, Ke / Rubin, Chanan / Grewal, Shiv I S

Science (New York, N.Y.)

2011 Volume 335, Issue 6064, Page(s) 96–100

Abstract	Facultative heterochromatin that changes during cellular differentiation coordinates regulated gene expression, but its assembly is poorly understood. Here, we describe facultative heterochromatin islands in fission yeast and show that their formation at meiotic genes requires factors that eliminate meiotic messenger RNAs (mRNAs) during vegetative growth. Blocking production of meiotic mRNA or loss of RNA elimination factors, including Mmi1 and Red1 proteins, abolishes heterochromatin islands. RNA elimination machinery is enriched at meiotic loci and interacts with Clr4/SUV39h, a methyltransferase involved in heterochromatin assembly. Heterochromatin islands disassemble in response to nutritional signals that induce sexual differentiation. This process involves the antisilencing factor Epe1, the loss of which causes dramatic increase in heterochromatic loci. Our analyses uncover unexpected regulatory roles for mRNA-processing factors that assemble dynamic heterochromatin to modulate gene expression.
MeSH term(s)	Cell Cycle Proteins/metabolism ; Chromatin Assembly and Disassembly ; Chromatin Immunoprecipitation ; Dynactin Complex ; Gene Expression Regulation, Fungal ; Genes, Fungal ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase ; Histones/metabolism ; Meiosis/genetics ; Methyltransferases/metabolism ; Microtubule Proteins/genetics ; Microtubule Proteins/metabolism ; Nitrogen/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; RNA Interference ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/growth & development ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; mRNA Cleavage and Polyadenylation Factors/metabolism
Chemical Substances	Cell Cycle Proteins ; Dynactin Complex ; Heterochromatin ; Histones ; Microtubule Proteins ; Mmi1 protein, S pombe ; Nuclear Proteins ; RNA, Fungal ; RNA, Messenger ; Schizosaccharomyces pombe Proteins ; Ssm4 protein, S pombe ; epe1 protein, S pombe ; mRNA Cleavage and Polyadenylation Factors ; mei4 protein, S pombe ; Methyltransferases (EC 2.1.1.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; clr4 protein, S pombe (EC 2.1.1.43) ; Nitrogen (N762921K75)
Language	English
Publishing date	2011-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1211651
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Article ; Online: Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast.

Fischer, Tamás / Cui, Bowen / Dhakshnamoorthy, Jothy / Zhou, Ming / Rubin, Chanan / Zofall, Martin / Veenstra, Timothy D / Grewal, Shiv I S

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

2009 Volume 106, Issue 22, Page(s) 8998–9003

Abstract: Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The ... ...

Abstract	Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The fission yeast Schizosaccharomyces pombe HP1 family members Chp2 and Swi6 are important for heterochromatin assembly and transcriptional silencing, but their precise roles are not fully understood. Here, we show that Swi6 and Chp2 associate with histone deacetylase (HDAC) protein complexes containing class I HDAC Clr6 and class II HDAC Clr3 (a component of Snf2/HDAC repressor complex), which are critical for transcriptional silencing of centromeric repeats targeted by the heterochromatin machinery. Mapping of RNA polymerase (Pol) II distribution in single and double mutant backgrounds revealed that Swi6 and Chp2 proteins and their associated HDAC complexes have overlapping functions in limiting Pol II occupancy across pericentromeric heterochromatin domains. The purified Swi6 fraction also contains factors involved in various chromosomal processes such as chromatin remodeling and DNA replication. Also, Swi6 copurifies with Mis4 protein, a cohesin loading factor essential for sister chromatid cohesion, and with centromere-specific histone H3 variant CENP-A, which is incorporated into chromatin in a heterochromatin-dependent manner. These analyses suggest that among other functions, HP1 proteins associate with chromatin-modifying factors that in turn cooperate to assemble repressive chromatin; thus, precluding accessibility of underlying DNA sequences to transcriptional machinery.
MeSH term(s)	Cell Cycle Proteins/metabolism ; Centromere/genetics ; Centromere/metabolism ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Polymerase II/metabolism ; Gene Silencing ; Heterochromatin/metabolism ; Histone Deacetylases/metabolism ; Repressor Proteins/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
Chemical Substances	CHP2 protein, S pombe ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Clr3 protein, S pombe ; Clr6 protein, S pombe ; Cnp1 protein, S pombe ; Heterochromatin ; MIS4 protein, S pombe ; Repressor Proteins ; Schizosaccharomyces pombe Proteins ; Swi6 protein, S pombe ; heterochromatin-specific nonhistone chromosomal protein HP-1 (107283-02-3) ; DNA Polymerase II (EC 2.7.7.7) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2009-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0813063106
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Article ; Online: Primate-specific evolution of an LDLR enhancer.

Wang, Qian-fei / Prabhakar, Shyam / Wang, Qianben / Moses, Alan M / Chanan, Sumita / Brown, Myles / Eisen, Michael B / Cheng, Jan-Fang / Rubin, Edward M / Boffelli, Dario

Genome biology

2006 Volume 7, Issue 8, Page(s) R68

Abstract: Background: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain.: Results: In this study we identified an anthropoid primate- ... ...

Abstract	Background: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. Results: In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Conclusion: Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
MeSH term(s)	Amino Acid Motifs/genetics ; Animals ; Base Sequence ; Cell Line ; Chromatin Immunoprecipitation ; Computational Biology ; Conserved Sequence/genetics ; DNA Primers ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Humans ; Mice ; Molecular Sequence Data ; Phylogeny ; Primates/genetics ; Receptors, LDL/genetics ; Sequence Alignment
Chemical Substances	DNA Primers ; Receptors, LDL
Language	English
Publishing date	2006
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/gb-2006-7-8-R68
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