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  • 1
    Publication Date: 2010-07-14
    Description: While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059551/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059551/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Wen -- Tanasa, Bogdan -- Tyurina, Oksana V -- Zhou, Tian Yuan -- Gassmann, Reto -- Liu, Wei Ting -- Ohgi, Kenneth A -- Benner, Chris -- Garcia-Bassets, Ivan -- Aggarwal, Aneel K -- Desai, Arshad -- Dorrestein, Pieter C -- Glass, Christopher K -- Rosenfeld, Michael G -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-09/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK018477-35/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-18/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-21/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 22;466(7305):508-12. doi: 10.1038/nature09272. Epub 2010 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20622854" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry/metabolism ; Cell Cycle/*physiology ; Cell Line ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/deficiency/genetics/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; HeLa Cells ; Histone Demethylases/chemistry/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/chemistry/*metabolism ; Host Cell Factor C1/genetics/metabolism ; Humans ; Lysine/*metabolism ; Methylation ; Multiprotein Complexes/chemistry/metabolism ; Phosphorylation ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Transcription Factors/chemistry/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-05-17
    Description: Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA) based on global nuclear run-on sequencing (GRO-seq) analysis, with a unique class apparently requiring no nucleosome remodelling to induce specific enhancer-promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117022/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Dong -- Garcia-Bassets, Ivan -- Benner, Chris -- Li, Wenbo -- Su, Xue -- Zhou, Yiming -- Qiu, Jinsong -- Liu, Wen -- Kaikkonen, Minna U -- Ohgi, Kenneth A -- Glass, Christopher K -- Rosenfeld, Michael G -- Fu, Xiang-Dong -- DK01847/DK/NIDDK NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK37949/DK/NIDDK NIH HHS/ -- GM049369/GM/NIGMS NIH HHS/ -- HG004659/HG/NHGRI NIH HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P01 DK074868-05/DK/NIDDK NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-10/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK018477-35/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-30/DK/NIDDK NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 GM049369/GM/NIGMS NIH HHS/ -- R01 GM049369-17/GM/NIGMS NIH HHS/ -- R01 HG004659/HG/NHGRI NIH HHS/ -- R01 HG004659-03/HG/NHGRI NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 HL065445-12/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-23/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-28/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 15;474(7351):390-4. doi: 10.1038/nature10006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21572438" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line, Tumor ; Cell Lineage ; Dihydrotestosterone/pharmacology ; Down-Regulation ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genome, Human/genetics ; HEK293 Cells ; Hepatocyte Nuclear Factor 3-alpha/deficiency/genetics/*metabolism ; Histones/metabolism ; Humans ; Kallikreins ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms/metabolism/pathology ; RNA, Small Interfering/genetics/metabolism ; RNA, Untranslated/*genetics ; Receptors, Androgen/*metabolism ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-10-25
    Description: Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behaviour and are not amenable to genetic manipulation. We propose that induced pluripotent stem (iPS) cells could be a unique biological resource to determine relevant phenotypical differences between human and NHPs, and that those differences could have potential adaptation and speciation value. Here we describe the generation and initial characterization of iPS cells from chimpanzees and bonobos as new tools to explore factors that may have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPS cells revealed differences in the regulation of long interspersed element-1 (L1, also known as LINE-1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. Decreased levels of L1-restricting factors APOBEC3B (also known as A3B) and PIWIL2 (ref. 7) in NHP iPS cells correlated with increased L1 mobility and endogenous L1 messenger RNA levels. Moreover, results from the manipulation of A3B and PIWIL2 levels in iPS cells supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPS cells in culture and may have also occurred in the germ line or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have continuing adaptive significance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064720/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marchetto, Maria C N -- Narvaiza, Inigo -- Denli, Ahmet M -- Benner, Christopher -- Lazzarini, Thomas A -- Nathanson, Jason L -- Paquola, Apua C M -- Desai, Keval N -- Herai, Roberto H -- Weitzman, Matthew D -- Yeo, Gene W -- Muotri, Alysson R -- Gage, Fred H -- AI074967/AI/NIAID NIH HHS/ -- GM084317/GM/NIGMS NIH HHS/ -- HG004659/HG/NHGRI NIH HHS/ -- MH08848/MH/NIMH NIH HHS/ -- MH094753/MH/NIMH NIH HHS/ -- NS075449/NS/NINDS NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01 MH088485/MH/NIMH NIH HHS/ -- R01 MH094753/MH/NIMH NIH HHS/ -- R01 MH095741/MH/NIMH NIH HHS/ -- R01 NS075449/NS/NINDS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):525-9. doi: 10.1038/nature12686. Epub 2013 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24153179" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/metabolism ; Cell Line ; Cell Shape ; Cytidine Deaminase/metabolism ; Evolution, Molecular ; Genome, Human/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Karyotyping ; Long Interspersed Nucleotide Elements/*genetics ; Mice, Nude ; Pan paniscus/*genetics/metabolism ; Pan troglodytes/*genetics/metabolism ; Pluripotent Stem Cells/cytology/*metabolism ; RNA, Messenger/analysis/genetics ; Sequence Analysis, RNA ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-05-07
    Description: Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jun -- Okamura, Daiji -- Li, Mo -- Suzuki, Keiichiro -- Luo, Chongyuan -- Ma, Li -- He, Yupeng -- Li, Zhongwei -- Benner, Chris -- Tamura, Isao -- Krause, Marie N -- Nery, Joseph R -- Du, Tingting -- Zhang, Zhuzhu -- Hishida, Tomoaki -- Takahashi, Yuta -- Aizawa, Emi -- Kim, Na Young -- Lajara, Jeronimo -- Guillen, Pedro -- Campistol, Josep M -- Esteban, Concepcion Rodriguez -- Ross, Pablo J -- Saghatelian, Alan -- Ren, Bing -- Ecker, Joseph R -- Izpisua Belmonte, Juan Carlos -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 May 21;521(7552):316-21. doi: 10.1038/nature14413. Epub 2015 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA. ; 1] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Integrated Genomics, La Jolla, California 92037, USA. ; Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA. ; 1] The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA [2] Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan. ; Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain. ; 1] Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain [2] Fundacion Pedro Guillen, Clinica Cemtro, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain. ; Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain. ; University of California, Davis, Davis, California 95616, USA. ; The Salk Institute for Biological Studies, Peptide Biology Laboratory, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25945737" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques/methods ; Cell Line ; *Chimera ; Embryonic Stem Cells/cytology ; Female ; Germ Layers/cytology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Male ; Mice ; Pan troglodytes ; Pluripotent Stem Cells/*cytology/metabolism ; Regenerative Medicine ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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