Research Topics
Genomes and Genes | A P WolffeSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
An asymmetric model for the nucleosome: a binding site for linker histones inside the DNA gyresD Pruss
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2710, USA
Science 274:614-7. 1996..This domain extends the path of the protein superhelix to one side of the core particle...
Masking and unmasking maternal mRNA. The role of polyadenylation, transcription, splicing, and nuclear historyF Meric
Laboratory of Molecular Embryology, NICHD, National Institutes of Health, Bethesda, Maryland 20892 5431, USA
J Biol Chem 271:30804-10. 1996..We suggest that the translational repression coupled to the transcription process will more effectively repress inappropriate gene expression in the oocyte and offer the potential to achieve a wider range of gene regulation...
What do linker histones do in chromatin?A P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 5430, USA
Bioessays 19:249-55. 1997..Surprisingly, H1 can both activate and repress transcription. We discuss how this architectural protein might accomplish this important regulatory role...
Histone acetyltransferases in controlP A Wade
Laboratory of Molecular Embryology, NICHHD, Bethesda, Maryland, 20892 5431, USA
Curr Biol 7:R82-4. 1997..The targeted post-translational modification of histones within regulatory nucleoprotein complexes provides an attractive mechanism for controlling transcription within a chromatin environment...
Chromatin disruption and modificationA P Wolffe
Laboratory of Molecular Embryology, Natational Institute of Child Health and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892 5431, USA
Nucleic Acids Res 27:711-20. 1999....
Histone acetylation: chromatin in actionP A Wade
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 5431, USA
Trends Biochem Sci 22:128-32. 1997..This review highlights these roles and discusses their significance for the maintenance of cell differentiation...
Activators and repressors: making use of chromatin to regulate transcriptionA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 5431, USA
Genes Cells 2:291-302. 1997..Variation in chromatin structure makes a major contribution to gene regulation. Here we discuss the enzymatic complexes and molecular machines that make use of chromatin to control transcription...
Transcription control: repressed repeats express themselvesA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892 5431, USA
Curr Biol 7:R796-8. 1997..Host defense mechanisms monitor repeated sequences in the genome, modulating their chromatin packaging and functional capabilities...
Packaging principle: how DNA methylation and histone acetylation control the transcriptional activity of chromatinA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5431, USA
J Exp Zool 282:239-44. 1998..These covalent modifications can have roles in both promoter-specific events and the global control of chromosomal activity. These regulatory functions are essential for vertebrate development...
Chromatin remodeling regulated by steroid and nuclear receptorsA P Wolffe
Laboratory of Molecular Embryology, Nat l Institute of Child Health and Human Development, Bethesda, MD 20892 5431, USA
Cell Res 7:127-42. 1997..The assembly of specific nucleoprotein architectures and targeted histone modification emerge as central controlling elements for gene expression...
Chromatin and chromosomal controls in developmentD Vermaak
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5431, USA
Dev Genet 22:1-6. 1998..Chromosomal position and nuclear compartmentalization represent important contributory factors in determining cell fate. These controls may explain many interesting and unexplored features of developmental systems...
Hormone action and chromatin remodellingD Robyr
Universite de Lausanne, Institut de Biologie Animale, Batiment de Biologie, Switzerland
Cell Mol Life Sci 54:113-24. 1998..Nucleosome positioning and targeted histone modification emerge as central controlling elements for gene expression...
Transcription: gene control by targeted histone acetylationA Imhof
Laboratory of Molecular Embryology, NICHD, NIH, Bethesda, Maryland 20892 5431, USA
Curr Biol 8:R422-4. 1998..This targeted modification is restricted to nucleosomes assembled on the promoters of Gcn5p-responsive genes...
Epigenetics: regulation through repressionA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892 5431, USA
Science 286:481-6. 1999..Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes...
Co-repressor complexes and remodelling chromatin for repressionA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892 5431, USA
Biochem Soc Trans 28:379-86. 2000..Remarkably, both of these complexes also contain methyl-CpG-binding proteins. This observation provides a molecular mechanism to integrate DNA methylation fully into gene control in vertebrates...
A Drosophila MBD family member is a transcriptional corepressor associated with specific genesE Ballestar
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, MD, USA
Eur J Biochem 268:5397-406. 2001..This banding pattern suggests gene-specific regulatory functions for dMBD-like and the Drosophila Mi-2 complex...
Functional analysis of the SIN3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyteD Vermaak
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 5431, USA
Mol Cell Biol 19:5847-60. 1999..However, the exogenous RPD3 deacetylase functions to repress transcription in the absence of a requirement for association with SIN3 or other targeted corepressors...
Transcriptional regulation: SWItching circuitryP A Wade
Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, Maryland 20892 5431, USA
Curr Biol 9:R221-4. 1999..How they do so is still mysterious, but recent studies indicate that they can be targeted to the nuclear infrastructure and to particular genes, where they cooperate with other enzymes to activate or repress transcription...
ATP-Dependent histone octamer mobilization and histone deacetylation mediated by the Mi-2 chromatin remodeling complexD Guschin
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, Maryland 20892 5431, USA
Biochemistry 39:5238-45. 2000..Surprisingly, ATPase activity had no effect on deacetylation of nucleosomal arrays...
Multiple ISWI ATPase complexes from xenopus laevis. Functional conservation of an ACF/CHRAC homologD Guschin
Laboratory of Molecular Embryology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 275:35248-55. 2000..This comprehensive biochemical characterization of ISWI underscores the evolutionary conservation of the ACF/CHRAC family...
Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylationP A Wade
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T Room 106, Bethesda, Maryland 20892, USA
Nat Genet 23:62-6. 1999..Our data substantiate the mechanistic link between DNA methylation, histone deacetylation and transcriptional silencing...
Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasiaF Magdinier
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 98:4990-5. 2001..Thus, methyl-CpG binding proteins and histone deacetylases appear to cooperate in vivo, with a dominant effect of DNA methylation toward histone acetylation, and repress expression of tumor suppressor genes hypermethylated in cancers...
Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteinsA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892
Bioessays 16:245-51. 1994..This review discusses the organization of the prokaryotic and eukaryotic Y-box proteins, how they interact with nucleic acids, and their biological roles, both proven and potential...
Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylaseJ Wong
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, MD 20892 5431, USA
EMBO J 17:520-34. 1998....
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcriptionP L Jones
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892 5431, USA
Nat Genet 19:187-91. 1998..These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin...
Xenopus NF-Y pre-sets chromatin to potentiate p300 and acetylation-responsive transcription from the Xenopus hsp70 promoter in vivoQ Li
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 5431, USA
EMBO J 17:6300-15. 1998..We suggest two steps in chromatin modification at the Xenopus hsp70 promoter: first the binding of NF-Y to the Y-boxes to pre-set chromatin and second the recruitment of p300 to modulate transcriptional activity...
Histone deacetylase: a regulator of transcriptionA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2710, USA
Science 272:371-2. 1996
Nuclear hormone receptor coregulators in action: diversity for shared tasksD Robyr
Institut de Biologie Animale, , , Switzerland
Mol Endocrinol 14:329-47. 2000
Purification and properties of the Xenopus Hat1 acetyltransferase: association with the 14-3-3 proteins in the oocyte nucleusA Imhof
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5431, USA
Biochemistry 38:13085-93. 1999..Following oocyte maturation and subsequent embryogenesis, the Hat1 enzyme is redistributed to the cytoplasm, where new histones are synthesized...
Functional consequences of Rett syndrome mutations on human MeCP2T M Yusufzai
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, MD 20892 5431, USA
Nucleic Acids Res 28:4172-9. 2000..Together, these results provide evidence of how Rett syndrome mutations can affect distinct functions of MeCP2 and give insight into these mutations that may contribute to the disease...
Chromatin remodeling by the thyroid hormone receptor in regulation of the thyroid-stimulating hormone alpha-subunit promoterT N Collingwood
Laboratory of Molecular Embryology, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 276:34227-34. 2001..In a comparison with the Xenopus TR beta A promoter, we found that the effects of these mutations on transactivation and chromatin remodeling were significantly more severe on the TSH alpha promoter...
Transcriptional repression by XPc1, a new Polycomb homolog in Xenopus laevis embryos, is independent of histone deacetylaseJ Strouboulis
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 5431, USA
Mol Cell Biol 19:3958-68. 1999....
SWItched-on mobilityD Guschin
Laboratory of Molecular Embryology National Institute of Child Health and Human Development National Institutes of Health Building 18T, Room 106, Bethesda, Maryland, 20892 5431, USA
Curr Biol 9:R742-6. 1999....
DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promotersK D Robertson
Laboratory of Molecular Embryology, NICHD, NIH, Bethesda, Maryland, USA
Nat Genet 25:338-42. 2000..These results establish a link between DNA methylation, histone deacetylase and sequence-specific DNA binding activity, as well as a growth-regulatory pathway that is disrupted in nearly all cancer cells...
A mouse Y box protein, MSY1, is associated with paternal mRNA in spermatocytesS R Tafuri
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
J Biol Chem 268:12213-20. 1993..These data suggest that the mouse Y box protein, MSY1, functions similarly to the FRGY2 protein in regulating the storage and translation of germ cell RNAs...
MeCP2 driven transcriptional repression in vitro: selectivity for methylated DNA, action at a distance and contacts with the basal transcription machineryN K Kaludov
Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892 5431, USA
Nucleic Acids Res 28:1921-8. 2000..The formation of such complexes reflects a local concentration of DNA-bound transcriptional repressor that may stabilize a state of repression even in the presence of exogenous transcriptional machinery...
Distinct roles for TBP and TBP-like factor in early embryonic gene transcription in XenopusG J Veenstra
Laboratory for Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
Science 290:2312-5. 2000..Because TBP and a TLF factor play complementary roles in embryonic development, our results indicate that although similar mechanistic roles exist in common, TBP and TLF function differentially to control transcription of specific genes...
Programming the transcriptional state of replicating methylated dnaW Stunkel
NICHD, National Institutes of Health, Bethesda, Maryland 20814, USA
J Biol Chem 276:20743-9. 2001..We conclude that "passive" demethylation at the replication fork is not simply dependent on the presence of DNA binding transcriptional activators...
Gene-selective developmental roles of general transcription factorsG J Veenstra
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
Trends Biochem Sci 26:665-71. 2001..However, this machinery is not of universal composition, and variants of the general transcription factors play specific roles in embryonic development, reflecting the constraints and requirements of developmental gene regulation...
Sin mutations of histone H3: influence on nucleosome core structure and functionH Kurumizaka
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5431, USA
Mol Cell Biol 17:6953-69. 1997..Thus, different Sin mutations in histone H3 alter the stability of histone-DNA interactions to various extents in the nucleosome while maintaining the fundamental architecture of the nucleosome and contributing to a common Sin phenotype...
Evidence for a shared structural role for HMG1 and linker histones B4 and H1 in organizing chromatinK Nightingale
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 2710, USA
EMBO J 15:548-61. 1996..However, neither histone B4 nor HMG1 influence the DNase I or hydroxyl radical digestion of DNA within the nucleosome core. We suggest that HMG1/2 and histone B4 have a shared structural role in organizing linker DNA in the nucleosome...
Transcriptional regulation in the context of chromatin structureA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 5431, USA
Essays Biochem 37:45-57. 2001..A major contributory factor to the functional specialization of chromatin is the capacity to target nucleosome modification and disruption...
Xenopus laevis B4, an intron-containing oocyte-specific linker histone-encoding geneH Cho
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892
Gene 143:233-8. 1994..Tissue-specific expression, a low copy number and presence of introns are all unusual features for vertebrate genes encoding linker histones...
Developmental roles for chromatin and chromosomal structureD Patterton
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892 2710, USA
Dev Biol 173:2-13. 1996....
The cDNA encoding Xenopus laevis heat-shock factor 1 (XHSF1): nucleotide and deduced amino-acid sequences, and properties of the encoded proteinD G Stump
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 2710, USA
Gene 160:207-11. 1995..Microinjection of XHSF1 mRNA into Xl oocytes leads to synthesis of XHSF1 which accumulates in the nucleus and selectively activates Xl phsp70p activity at 18 degrees C...
Isolation of a potentially functional Y-box protein (MSY-1) processed pseudogene from mouse: evolutionary relationships within the EF1A/dbpB/YB-1 gene familyM Familari
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
Gene 141:255-9. 1994..We find that the mouse genome contains many DNA sequences with homology to a cDNA encoding the DNA-binding domain of the Y-box proteins. We estimate that there are at least 15 copies per haploid genome...
How does DNA methylation repress transcription?S U Kass
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 5431, USA
Trends Genet 13:444-9. 1997..Specialized nucleosomes also provide a potential molecular mechanism for the stable propagation of DNA methylation-dependent transcriptional silencing through cell division...
Role of chromatin and Xenopus laevis heat shock transcription factor in regulation of transcription from the X. laevis hsp70 promoter in vivoN Landsberger
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 2710, USA
Mol Cell Biol 15:6013-24. 1995..We suggest that chromatin assembly has a physiological role in establishing a transcriptionally repressed state on the Xenopus hsp70 promoter in vivo...
Thyroid hormone receptor, v-ErbA, and chromatinA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5431, USA
Vitam Horm 58:449-92. 2000..This system provides an exceptionally useful paradigm for investigating the structural and functional consequences of targeted chromatin modification...
Targeting chromatin disruption: Transcription regulators that acetylate histonesA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, 20892-2710, USA
Cell 84:817-9. 1996
A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPaseP A Wade
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Curr Biol 8:843-6. 1998..This association of a histone deacetylase with a Snf2 superfamily ATPase suggests a functional link between these two disparate classes of chromatin regulators...
Hanging on to histones. ChromatinA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Building 6, Room B1A13, National Institutes of Health, Bethesda, Maryland 20892 2710, USA
Curr Biol 6:234-7. 1996....
A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2H Ge
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Cell 2:751-9. 1998..Together, these observations suggest that, in addition to functioning as a transcriptional coactivator, p52 may also act as an adaptor to coordinate pre-mRNA splicing and transcriptional activation of class II genes...
Constitutive genomic methylation during embryonic development of XenopusG J Veenstra
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
Biochim Biophys Acta 1521:39-44. 2001..The methylation status of specific loci is independent of the temporal expression profile. The observations have profound implications for the regulation of early embryonic gene regulation and genome function...
Deviant nucleosomes: the functional specialization of chromatinA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2710, USA
Trends Genet 12:58-62. 1996..Their assembly into nucleosomal structures confers specialized functions to individual chromosomal domains...
DNA methylation in health and diseaseK D Robertson
Epigenetic Gene Regulation and Cancer Section, NCI, NIH, Building 41, 41 Library Drive, Bethesda, Maryland 20892 5431, USA
Nat Rev Genet 1:11-9. 2000..Recent advances have connected DNA methylation to chromatin-remodelling enzymes, and understanding this link will be central to the design of new therapeutic tools...
The Y-box factors: a family of nucleic acid binding proteins conserved from Escherichia coli to manA P Wolffe
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892
New Biol 4:290-8. 1992..Biologically they have roles in both transcriptional and translational regulation. Conserved through evolution from prokaryotic to eukaryotic organisms they represent a new family of nucleic acid binding proteins...
DNA gyrase, CS7.4, and the cold shock response in Escherichia coliP G Jones
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892
J Bacteriol 174:5798-802. 1992....
Common sequence and structural features in the heat-shock factor and Ets families of DNA-binding domainsD Landsman
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Trends Biochem Sci 20:225-6. 1995
Transcriptional control. Sinful repressionA P Wolffe
Nature 387:16-7. 1997
Xenopus Y-box transcription factors: molecular cloning, functional analysis and developmental regulationS R Tafuri
Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892
Proc Natl Acad Sci U S A 87:9028-32. 1990..We identify protamine-like regions that are present within this family of transcription factors, suggesting that they use unusual means of binding to DNA...
Chromatin structure and phaseolin gene regulationG Li
Sangamo Biosciences Inc, Point Richmond Technology Center, Richmond, CA 94804, USA
Plant Mol Biol 46:121-9. 2001..These concepts, and the possible modular nature of phas expression, are summarized together with speculations concerning the re-establishment of the nucleosome over the phas promoter during terminal stages of embryogenesis...
Chromatin remodeling: why it is important in cancerA P Wolffe
Sangamo Biosciences Inc, Point Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
Oncogene 20:2988-90. 2001..Mistargeting of these enzymes leads to tumorigenesis, but inhibition of their activity presents a novel approach to therapy...
Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymesL A Boyer
Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 275:18864-70. 2000..We propose that ATP-dependent chromatin remodeling enzymes share a common reaction mechanism and that a key distinction between complexes is in their mode of regulation or recruitment...
Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor AP Q Liu
Sangamo BioSciences Incorporated, Richmond, California 94804, USA
J Biol Chem 276:11323-34. 2001..Our strategy provides a novel approach for dissecting the requirements for gene regulation at a distance without altering the DNA sequence of the endogenous target locus...
Deinduction of transcription of Xenopus 74-kDa albumin genes and destabilization of mRNA by estrogen in vivo and in hepatocyte culturesA P Wolffe
Eur J Biochem 146:489-96. 1985....
Targeted regulation of imprinted genes by synthetic zinc-finger transcription factorsY Jouvenot
Sangamo BioSciences, Inc, Point Richmond Tech Center, Richmond, CA 94804, USA
Gene Ther 10:513-22. 2003....
