Rb Interacts with Histone Deacetylase to Repress Transcription

Previously, we found that Rb can actively repress transcription of cell cycle genes by binding and inactivating transcription factors at the promoter. Here, we demonstrate that Rb can also repress transcription of endogenous cell cycle genes containing E2F sites through recruitment of histone deacetylase, which deacetylates histones on the promoter, thereby promoting formation of nucleosomes that inhibit transcription. These two mechanisms of repression by Rb are selective-some promoters and transcription factors are blocked by this recruitment of histone deacetylase, whereas others are resistant to histone deacetylase activity and are repressed directly by inhibition of transcription factors.

[1]  R. Eisenman,et al.  Mad-max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3 , 1995, Cell.

[2]  F. Winston,et al.  Nucleosomes and transcription: recent lessons from genetics. , 1997, Current opinion in genetics & development.

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

[4]  F. Kaye,et al.  A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[5]  L. Kedes,et al.  Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C , 1997, Molecular and cellular biology.

[6]  A. Giordano,et al.  p300 is required for MyoD‐dependent cell cycle arrest and muscle‐specific gene transcription , 1997, The EMBO journal.

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

[8]  M. Beato,et al.  The hormone responsive region of mouse mammary tumor virus positions a nucleosome and precludes access of nuclear factor I to the promoter , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[9]  D. Livingston,et al.  Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. , 1996, Genes & development.

[10]  S. Weintraub,et al.  Mechanism of active transcriptional repression by the retinoblastoma protein , 1995, Nature.

[11]  J. Darnell,et al.  Two contact regions between Stat1 and CBP/p300 in interferon γ signaling , 1996 .

[12]  S. Bhattacharya,et al.  Cooperation of Stat2 and p300/CBP in signalling induced by interferon-α , 1996, Nature.

[13]  R. Weinberg,et al.  The retinoblastoma protein and cell cycle control , 1995, Cell.

[14]  C. Allis,et al.  A simplified formaldehyde fixation and immunoprecipitation technique for studying protein-DNA interactions. , 1991, Analytical biochemistry.

[15]  D. Trouche,et al.  E2F1 and E1A(12S) have a homologous activation domain regulated by RB and CBP. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  W. Sellers,et al.  A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Monika Tsai-Pflugfelder,et al.  A proline-rich TGF-beta-responsive transcriptional activator interacts with histone H3. , 1995, Genes & development.

[18]  A. Stein,et al.  Micrococcal nuclease digestion of nuclei reveals extended nucleosome ladders having anomalous DNA lengths for chromatin assembled on non-replicating plasmids in transfected cells. , 1994, Nucleic acids research.

[19]  R. Kobayashi,et al.  Nucleosome Assembly by a Complex of CAF-1 and Acetylated Histones H3/H4 , 1996, Cell.

[20]  E. Lam,et al.  DP and E2F proteins: coordinating transcription with cell cycle progression. , 1994, Current opinion in cell biology.

[21]  W. Kaelin,et al.  The cellular effects of E2F overexpression. , 1996, Current topics in microbiology and immunology.

[22]  S. Schreiber,et al.  Nuclear Receptor Repression Mediated by a Complex Containing SMRT, mSin3A, and Histone Deacetylase , 1997, Cell.

[23]  D. Dean,et al.  ZEB, a vertebrate homolog of Drosophila Zfh‐1, is a negative regulator of muscle differentiation , 1997, The EMBO journal.

[24]  Joseph R. Nevins,et al.  The E2F transcription factor is a cellular target for the RB protein , 1991, Cell.

[25]  C. Ingles,et al.  Direct transcriptional repression by pRB and its reversal by specific cyclins , 1995, Molecular and cellular biology.

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

[27]  M. Ewen,et al.  Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. , 1993, Genes & development.

[28]  Y. Qian,et al.  A retinoblastoma-binding protein related to a negative regulator of Ras in yeast , 1993, Nature.

[29]  G. Nabel,et al.  Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator , 1997, Science.

[30]  R. Kobayashi,et al.  The p55 subunit of Drosophila chromatin assembly factor 1 is homologous to a histone deacetylase-associated protein , 1996, Molecular and cellular biology.

[31]  Sushovan Guha,et al.  The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest , 1994, Cell.

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

[33]  S. Schreiber,et al.  A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p , 1996, Science.

[34]  B. Howard,et al.  A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A , 1996, Nature.

[35]  S. Weintraub,et al.  Retinoblastoma protein switches the E2F site from positive to negative element , 1992, Nature.

[36]  R. Tjian,et al.  SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein. , 1996, Genes & development.

[37]  N. Dyson,et al.  pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. , 1997, Genes & development.

[38]  J. Nevins,et al.  E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. , 1992, Science.

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

[40]  C. Allis,et al.  Histone Acetylation and Chromatin Assembly: A Single Escort, Multiple Dances? , 1996, Cell.

[41]  A. Wolffe,et al.  Nucleosomes and Transcription , 1997 .

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

[43]  D. Livingston,et al.  The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[44]  P. Starostik,et al.  Transcriptional repression and growth suppression by the p107 pocket protein , 1996, Molecular and cellular biology.

[45]  J B Lawrence,et al.  Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. , 1994, Genes & development.

[46]  P. Farnham,et al.  Introduction to the E2F family: protein structure and gene regulation. , 1996, Current topics in microbiology and immunology.

[47]  D. Reinberg,et al.  Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex , 1997, Cell.

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

[49]  P. Robbins,et al.  The retinoblastoma-susceptibility gene product binds directly to the human TATA-binding protein-associated factor TAFII250. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[51]  J. Nevins,et al.  Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals , 1997, Molecular and cellular biology.

[52]  P. Starostik,et al.  The Rb family contains a conserved cyclin-dependent-kinase-regulated transcriptional repressor motif , 1996, Molecular and cellular biology.

[53]  R. Eisenman,et al.  A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. , 1993, Genes & development.

[54]  M. Montminy,et al.  Role of CBP/P300 in nuclear receptor signalling , 1996, Nature.

[55]  D. Dean,et al.  Domains A and B in the Rb pocket interact to form a transcriptional repressor motif , 1996, Molecular and cellular biology.

[56]  Ya-Li Yao,et al.  Isolation and Characterization of cDNAs Corresponding to an Additional Member of the Human Histone Deacetylase Gene Family* , 1997, The Journal of Biological Chemistry.

[57]  G. Jenster,et al.  Steroid receptor induction of gene transcription: a two-step model. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[58]  J. Darnell,et al.  Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. , 1996, Proceedings of the National Academy of Sciences of the United States of America.