Trichostatin A causes selective loss of DNA methylation in Neurospora.

Both DNA methylation and hypoacetylation of core histones are frequently associated with repression of gene expression. Possible connections between these processes were investigated by taking advantage of genes controlled by methylation in Neurospora crassa. Trichostatin A (TSA), a potent inhibitor of histone deacetylase, derepressed a copy of hph that was repressed by DNA methylation which resulted from repeat-induced point mutation (RIP) acting on sequences flanking hph. Derepression by TSA was comparable to derepression by the inhibitor of DNA methylation, 5-azacytidine. TSA treatment also repressed an allele of am whose expression depends on methylation of an adjacent transposon, Tad. DNA methylation in the hph and Tad/am regions was greatly reduced by TSA treatment. TSA also caused hypomethylation of other methylated alleles of am generated by RIP. In contrast, TSA did not affect methylation of several other methylated genomic sequences examined, including the nucleolar rDNA and the inactivated transposon PuntRIP1. Several possible models are discussed for the observed selective demethylation induced by TSA. The implication that acetylation of chromatin proteins can directly or indirectly control DNA methylation raises the possibility that connections between protein acetylation and DNA methylation result in self-reinforcing epigenetic states.

[1]  J. Strouboulis,et al.  Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription , 1998, Nature Genetics.

[2]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[3]  H. Chen,et al.  The Neurospora aab-1 gene encodes a CCAAT binding protein homologous to yeast HAP5. , 1998, Genetics.

[4]  B. Turner,et al.  Transient Inhibition of Histone Deacetylation Alters the Structural and Functional Imprint at Fission Yeast Centromeres , 1997, Cell.

[5]  E. Verdin,et al.  Histone acetyltransferases regulate HIV-1 enhancer activity in vitro. , 1997, Genes & development.

[6]  T. Sakai,et al.  Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites. , 1997, Biochemical and biophysical research communications.

[7]  M. Hampsey.  A SAGA of histone acetylation and gene expression. , 1997, Trends in genetics : TIG.

[8]  A. Wolffe,et al.  How does DNA methylation repress transcription? , 1997, Trends in genetics : TIG.

[9]  M. Grunstein.  Histone acetylation in chromatin structure and transcription , 1997, Nature.

[10]  E. Selker,et al.  DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. , 1997, Genes & development.

[11]  Z. Chen,et al.  Epigenetic silencing of RNA polymerase I transcription: a role for DNA methylation and histone modification in nucleolar dominance. , 1997, Genes & development.

[12]  R. Evans,et al.  Nuclear Receptor Coactivator ACTR Is a Novel Histone Acetyltransferase and Forms a Multimeric Activation Complex with P/CAF and CBP/p300 , 1997, Cell.

[13]  C. Walsh,et al.  Cytosine methylation and the ecology of intragenomic parasites. , 1997, Trends in genetics : TIG.

[14]  R. Jaenisch.  DNA methylation and imprinting: why bother? , 1997, Trends in genetics : TIG.

[15]  E. Selker.  Epigenetic phenomena in filamentous fungi: useful paradigms or repeat-induced confusion? , 1997, Trends in genetics : TIG.

[16]  J. Irelan,et al.  Cytosine methylation associated with repeat-induced point mutation causes epigenetic gene silencing in Neurospora crassa. , 1997, Genetics.

[17]  J. Dong,et al.  Reactivation of silenced, virally transduced genes by inhibitors of histone deacetylase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Wen‐Ming Yang,et al.  Histone Deacetylases Associated with the mSin3 Corepressor Mediate Mad Transcriptional Repression , 1997, Cell.

[19]  K. Struhl,et al.  Repression by Ume6 Involves Recruitment of a Complex Containing Sin3 Corepressor and Rpd3 Histone Deacetylase to Target Promoters , 1997, Cell.

[20]  M. Pazin,et al.  What's Up and Down with Histone Deacetylation and Transcription? , 1997, Cell.

[21]  Stuart L Schreiber,et al.  Histone Deacetylase Activity Is Required for Full Transcriptional Repression by mSin3A , 1997, Cell.

[22]  L. Chin,et al.  Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression , 1997, nature.

[23]  C. Glass,et al.  A complex containing N-CoR, mSln3 and histone deacetylase mediates transcriptional repression , 1997, nature.

[24]  A. Wolffe,et al.  Histone acetylation: chromatin in action. , 1997, Trends in biochemical sciences.

[25]  Andrew J. Bannister,et al.  The TAFII250 Subunit of TFIID Has Histone Acetyltransferase Activity , 1996, Cell.

[26]  B. Turner,et al.  X-Inactivation and histone H4 acetylation in embryonic stem cells. , 1996, Developmental biology.

[27]  M. Grunstein,et al.  HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  B M Turner,et al.  Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern , 1996, Molecular and cellular biology.

[29]  E. Selker,et al.  Epigenetic control of a transposon-inactivated gene in Neurospora is dependent on DNA methylation. , 1996, Genetics.

[30]  C. Allis,et al.  Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation , 1996, Cell.

[31]  E. Selker,et al.  Control and Function of DNA Methylation in Neurospora crassa , 1996 .

[32]  E. Selker,et al.  DNA methylation associated with repeat-induced point mutation in Neurospora crassa , 1995, Molecular and cellular biology.

[33]  B. Turner,et al.  Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation‐dependent but transcription‐independent manner. , 1995, The EMBO journal.

[34]  K. A. Walker,et al.  Epigenetic Gene Inactivation Induced by a Cis-acting Methylation Center (*) , 1995, The Journal of Biological Chemistry.

[35]  C. J. Roberts,et al.  Mutations affecting the biosynthesis of S-adenosylmethionine cause reduction of DNA methylation in Neurospora crassa. , 1995, Nucleic acids research.

[36]  J. Irelan,et al.  High frequency repeat-induced point mutation (RIP) is not associated with efficient recombination in Neurospora. , 1994, Genetics.

[37]  A. Bird,et al.  Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. , 1994, Genes & development.

[38]  Z. Siegfried,et al.  Spl elements protect a CpG island from de novo methylation , 1994, Nature.

[39]  C. Hsieh,et al.  Dependence of transcriptional repression on CpG methylation density , 1994, Molecular and cellular biology.

[40]  M. Kuroda,et al.  Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. , 1994, Genes & development.

[41]  C. J. Roberts,et al.  Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation. , 1993, Science.

[42]  E. Selker,et al.  Dense nonsymmetrical DNA methylation resulting from repeat-induced point mutation in Neurospora. , 1993, Science.

[43]  B. Turner,et al.  The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression , 1993, Cell.

[44]  J. Rossignol,et al.  Methylation induced premeiotically in Ascobolus: coextension with DNA repeat lengths and effect on transcript elongation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Merigan Wh.  Colour vision: human V4? , 1993, Current biology : CB.

[46]  J. Broach,et al.  Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. , 1993, Genes & development.

[47]  P. Garrett-engele,et al.  Dissection of the signal for DNA methylation in the zeta-eta region of Neurospora. , 1993, Cold Spring Harbor symposia on quantitative biology.

[48]  G. Thireos,et al.  Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. , 1992, The EMBO journal.

[49]  Adrian Bird,et al.  The essentials of DNA methylation , 1992, Cell.

[50]  B. Turner,et al.  Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei , 1992, Cell.

[51]  T. R. Hebbes,et al.  Histone acetylation and globin gene switching. , 1992, Nucleic acids research.

[52]  Adrian Bird,et al.  Alternative chromatin structure at CpG islands , 1990, Cell.

[53]  A. Csordás,et al.  On the biological role of histone acetylation. , 1990, The Biochemical journal.

[54]  E. Selker.  Premeiotic instability of repeated sequences in Neurospora crassa. , 1990, Annual review of genetics.

[55]  E. Selker,et al.  Repeat-induced G-C to A-T mutations in Neurospora. , 1989, Science.

[56]  E. Selker,et al.  DNA sequence duplications trigger gene inactivation in Neurospora crassa. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[57]  E. Selker,et al.  Rearrangement of duplicated DNA in specialized cells of Neurospora , 1987, Cell.

[58]  A. Graessmann,et al.  Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[59]  D. Henner,et al.  Transformation of Aspergillus nidulans with the hygromycin-resistance gene, hph. , 1987, Gene.

[60]  R. Metzenberg,et al.  Reversal of a Neurospora translocation by crossing over involving displaced rDNA, and methylation of the rDNA segments that result from recombination. , 1986, Genetics.

[61]  Howard Cedar,et al.  DNA methylation affects the formation of active chromatin , 1986, Cell.