Large-scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 1999 Jun 29

PMID 10385516

Citations 146

Authors

T Tumbar

G Sudlow

A S Belmont

Affiliations

Soon will be listed here.

Abstract

Analysis of the relationship between transcriptional activators and chromatin organization has focused largely on lower levels of chromatin structure. Here we describe striking remodeling of large-scale chromatin structure induced by a strong transcriptional activator. A VP16-lac repressor fusion protein targeted the VP16 acidic activation domain to chromosome regions containing lac operator repeats. Targeting was accompanied by increased transcription, localized histone hyperacetylation, and recruitment of at least three different histone acetyltransferases. Observed effects on large-scale chromatin structure included unfolding of a 90-Mbp heterochromatic chromosome arm into an extended 25-40-micrometers chromonema fiber, remodeling of this fiber into a novel subnuclear domain, and propagation of large-scale chromatin unfolding over hundreds of kilobase pairs. These changes in large-scale chromatin structure occurred even with inhibition of ongoing transcription by alpha-amanitin. Our results suggest a functional link between recruitment of the transcriptional machinery and changes in large-scale chromatin structure. Based on the observed long-range propagation of changes in large-scale chromatin structure, we suggest a possible rationale for the observed clustering of housekeeping genes within Mbp-sized chromosome bands.

Citing Articles

The opportunities and challenges of epigenetic approaches to manage herpes simplex infections.

Saddoris S, Schang L Expert Rev Anti Infect Ther. 2024; 22(12):1123-1142.

PMID: 39466139 PMC: 11634640. DOI: 10.1080/14787210.2024.2420329.

Fusion of a rice endogenous -methylpurine DNA glycosylase to a plant adenine base transition editor ABE8e enables A-to-K base editing in rice plants.

Li Y, Li S, Li C, Zhang C, Yan L, Li J aBIOTECH. 2024; 5(2):127-139.

PMID: 38974865 PMC: 11224198. DOI: 10.1007/s42994-024-00138-8.

Histone H2A variant H2A.B is enriched in transcriptionally active and replicating HSV-1 lytic chromatin.

Flores Cortes E, Saddoris S, Owens A, Gibeault R, Depledge D, Schang L J Virol. 2024; 98(4):e0201523.

PMID: 38451083 PMC: 11019955. DOI: 10.1128/jvi.02015-23.

Engineering a plant A-to-K base editor with improved performance by fusion with a transactivation module.

Li Y, Li S, Li C, Zhang C, Yan L, Li J Plant Commun. 2023; 4(6):100667.

PMID: 37528582 PMC: 10721455. DOI: 10.1016/j.xplc.2023.100667.

Structural insights into p300 regulation and acetylation-dependent genome organisation.

Ibrahim Z, Wang T, Destaing O, Salvi N, Hoghoughi N, Chabert C Nat Commun. 2022; 13(1):7759.

PMID: 36522330 PMC: 9755262. DOI: 10.1038/s41467-022-35375-2.

References

Chan P . Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with selected cytotoxic agents (studies of B23-translocation mechanism). Exp Cell Res. 1992; 203(1):174-81. DOI: 10.1016/0014-4827(92)90053-b. View

Kuo M, Allis C . Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays. 1998; 20(8):615-26. DOI: 10.1002/(SICI)1521-1878(199808)20:8<615::AID-BIES4>3.0.CO;2-H. View

Svaren J, Horz W . Histones, nucleosomes and transcription. Curr Opin Genet Dev. 1993; 3(2):219-25. DOI: 10.1016/0959-437x(93)90026-l. View

Wansink D, Schul W, van der Kraan I, van Steensel B, VAN Driel R, de Jong L . Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus. J Cell Biol. 1993; 122(2):283-93. PMC: 2119648. DOI: 10.1083/jcb.122.2.283. View

Goodrich J, Hoey T, Thut C, Admon A, Tjian R . Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor TFIIB. Cell. 1993; 75(3):519-30. DOI: 10.1016/0092-8674(93)90386-5. View

Hebbes T, Clayton A, Thorne A, Crane-Robinson C . Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken beta-globin chromosomal domain. EMBO J. 1994; 13(8):1823-30. PMC: 395022. DOI: 10.1002/j.1460-2075.1994.tb06451.x. View

Dillon N, Grosveld F . Chromatin domains as potential units of eukaryotic gene function. Curr Opin Genet Dev. 1994; 4(2):260-4. DOI: 10.1016/s0959-437x(05)80053-x. View

Belmont A, Bruce K . Visualization of G1 chromosomes: a folded, twisted, supercoiled chromonema model of interphase chromatid structure. J Cell Biol. 1994; 127(2):287-302. PMC: 2120203. DOI: 10.1083/jcb.127.2.287. View

Xiao H, Pearson A, Coulombe B, Truant R, Zhang S, Regier J . Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53. Mol Cell Biol. 1994; 14(10):7013-24. PMC: 359231. DOI: 10.1128/mcb.14.10.7013-7024.1994. View

10.

Chuang P, Albertson D, Meyer B . DPY-27:a chromosome condensation protein homolog that regulates C. elegans dosage compensation through association with the X chromosome. Cell. 1994; 79(3):459-74. DOI: 10.1016/0092-8674(94)90255-0. View

11.

Cremer T, Kurz A, Zirbel R, Dietzel S, Rinke B, Schrock E . Role of chromosome territories in the functional compartmentalization of the cell nucleus. Cold Spring Harb Symp Quant Biol. 1993; 58:777-92. DOI: 10.1101/sqb.1993.058.01.085. View

12.

Marcus G, Silverman N, Berger S, Horiuchi J, Guarente L . Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. EMBO J. 1994; 13(20):4807-15. PMC: 395419. DOI: 10.1002/j.1460-2075.1994.tb06806.x. View

13.

Barlev N, Candau R, Wang L, Darpino P, Silverman N, Berger S . Characterization of physical interactions of the putative transcriptional adaptor, ADA2, with acidic activation domains and TATA-binding protein. J Biol Chem. 1995; 270(33):19337-44. DOI: 10.1074/jbc.270.33.19337. View

14.

Walter J, Biggin M . DNA binding specificity of two homeodomain proteins in vitro and in Drosophila embryos. Proc Natl Acad Sci U S A. 1996; 93(7):2680-5. PMC: 39690. DOI: 10.1073/pnas.93.7.2680. View

15.

Brownell J, Zhou J, Ranalli T, Kobayashi R, Edmondson D, Roth S . Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996; 84(6):843-51. DOI: 10.1016/s0092-8674(00)81063-6. View

16.

Kingston R, Bunker C, Imbalzano A . Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 1996; 10(8):905-20. DOI: 10.1101/gad.10.8.905. View

17.

Gupta R, Emili A, Pan G, Xiao H, Shales M, GREENBLATT J . Characterization of the interaction between the acidic activation domain of VP16 and the RNA polymerase II initiation factor TFIIB. Nucleic Acids Res. 1996; 24(12):2324-30. PMC: 145954. DOI: 10.1093/nar/24.12.2324. View

18.

Nguyen V, Giannoni F, Dubois M, Seo S, Vigneron M, Kedinger C . In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. Nucleic Acids Res. 1996; 24(15):2924-9. PMC: 146057. DOI: 10.1093/nar/24.15.2924. View

19.

Martin D, Fiering S, Groudine M . Regulation of beta-globin gene expression: straightening out the locus. Curr Opin Genet Dev. 1996; 6(4):488-95. DOI: 10.1016/s0959-437x(96)80072-4. View

20.

Wansink D, Sibon O, Cremers F, VAN Driel R, de Jong L . Ultrastructural localization of active genes in nuclei of A431 cells. J Cell Biochem. 1996; 62(1):10-8. DOI: 10.1002/(sici)1097-4644(199607)62:1<10::aid-jcb2>3.0.co;2-4. View