HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy

In human transcriptional regulation, DNA-sequence-specific factors can associate with intermediaries that orchestrate interactions with a diverse set of chromatin-modifying enzymes. One such intermediary is HCFC1 (also known as HCF-1). HCFC1, first identified in herpes simplex virus transcription, has a poorly defined role in cellular transcriptional regulation. We show here that, in HeLa cells, HCFC1 is observed bound to 5400 generally active CpG-island promoters. Examination of the DNA sequences underlying the HCFC1-binding sites revealed three sequence motifs associated with the binding of (1) ZNF143 and THAP11 (also known as Ronin), (2) GABP, and (3) YY1 sequence-specific transcription factors. Subsequent analysis revealed colocalization of HCFC1 with these four transcription factors at ∼90% of the 5400 HCFC1-bound promoters. These studies suggest that a relatively small number of transcription factors play a major role in HeLa-cell transcriptional regulation in association with HCFC1.

[1]  X. Chen,et al.  Zfp143 Regulates Nanog Through Modulation of Oct4 Binding , 2008, Stem cells.

[2]  T. Kristie,et al.  A Protein Sequestering System Reveals Control of Cellular Programs by the Transcriptional Coactivator HCF-1*♦ , 2004, Journal of Biological Chemistry.

[3]  Stephen S. Taylor,et al.  Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability , 2004, Journal of Cell Science.

[4]  Anindya Dutta,et al.  The Deubiquitinating Enzyme BAP1 Regulates Cell Growth via Interaction with HCF-1* , 2009, The Journal of Biological Chemistry.

[5]  Philip Lijnzaad,et al.  The Ensembl genome database project , 2002, Nucleic Acids Res..

[6]  Raja Jothi,et al.  Genome-wide identification of in vivo protein–DNA binding sites from ChIP-Seq data , 2008, Nucleic acids research.

[7]  H. Stunnenberg,et al.  Monoclonal antibodies directed against the amino-terminal domain of human TBP cross-react with TBP from other species. , 1996, Hybridoma.

[8]  Thomas A. Milne,et al.  WDR5 Associates with Histone H3 Methylated at K4 and Is Essential for H3 K4 Methylation and Vertebrate Development , 2005, Cell.

[9]  T. Kristie,et al.  The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP , 2000, The EMBO journal.

[10]  Panayiotis V. Benos,et al.  STAMP: a web tool for exploring DNA-binding motif similarities , 2007, Nucleic Acids Res..

[11]  M. Bycroft,et al.  Solution structure of the nonmethyl‐CpG‐binding CXXC domain of the leukaemia‐associated MLL histone methyltransferase , 2006, The EMBO journal.

[12]  Francisco Antequera,et al.  CpG islands as genomic footprints of promoters that are associated with replication origins , 1999, Current Biology.

[13]  S. Tyagi,et al.  Role of Host Cell Factor-1 in cell cycle regulation. , 2012, Transcription.

[14]  R. Tjian,et al.  Orchestrated response: a symphony of transcription factors for gene control. , 2000, Genes & development.

[15]  Robert S. Illingworth,et al.  Orphan CpG Islands Identify Numerous Conserved Promoters in the Mammalian Genome , 2010, PLoS genetics.

[16]  Charles Elkan,et al.  Fitting a Mixture Model By Expectation Maximization To Discover Motifs In Biopolymer , 1994, ISMB.

[17]  Patrick T. Reilly,et al.  Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells , 2001, Molecular and Cellular Biology.

[18]  P. Carbon,et al.  Flexible Zinc Finger Requirement for Binding of the Transcriptional Activator Staf to U6 Small Nuclear RNA and tRNASec Promoters* , 1999, The Journal of Biological Chemistry.

[19]  G. Hart,et al.  The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and Is a Critical Regulator of Gene Expression , 2010, Molecular and Cellular Biology.

[20]  A. Visel,et al.  ChIP-seq accurately predicts tissue-specific activity of enhancers , 2009, Nature.

[21]  Winship Herr,et al.  The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. , 2003, Trends in biochemical sciences.

[22]  V. Misra,et al.  The Herpesvirus Transactivator VP16 Mimics a Human Basic Domain Leucine Zipper Protein, Luman, in Its Interaction with HCF , 1998, Journal of Virology.

[23]  Winship Herr,et al.  E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. , 2007, Molecular cell.

[24]  R. Young,et al.  Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. , 2010, Genes & development.

[25]  W. Herr,et al.  Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. , 2003, Genes & development.

[26]  C. V. Jongeneel,et al.  Indexing Strategies for Rapid Searches of Short Words in Genome Sequences , 2007, PloS one.

[27]  J. D. den Dunnen,et al.  Genome-wide assessment of differential roles for p300 and CBP in transcription regulation , 2010, Nucleic acids research.

[28]  W. Herr,et al.  Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP. , 1997, Genes & development.

[29]  P. Carbon,et al.  Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription , 2010, Nucleic acids research.

[30]  Gordon K Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2011 .

[31]  Alexander E. Kel,et al.  TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes , 2005, Nucleic Acids Res..

[32]  Tony Kouzarides,et al.  Spatial Distribution of Di- and Tri-methyl Lysine 36 of Histone H3 at Active Genes* , 2005, Journal of Biological Chemistry.

[33]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[34]  P. Schenk,et al.  Improved high-level expression system for eukaryotic genes in Escherichia coli using T7 RNA polymerase and rare ArgtRNAs. , 1995, BioTechniques.

[35]  S. Mott,et al.  The Ets transcription factor GABP is required for cell-cycle progression , 2007, Nature Cell Biology.

[36]  W. Herr,et al.  O-GlcNAc Transferase Catalyzes Site-Specific Proteolysis of HCF-1 , 2011, Cell.

[37]  W. Herr,et al.  Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF‐1 , 2003, The EMBO journal.

[38]  M. Washburn,et al.  CHD8 Associates with Human Staf and Contributes to Efficient U6 RNA Polymerase III Transcription , 2007, Molecular and Cellular Biology.

[39]  Michael Gribskov,et al.  Combining evidence using p-values: application to sequence homology searches , 1998, Bioinform..

[40]  Li-Fang Chu,et al.  Ronin Is Essential for Embryogenesis and the Pluripotency of Mouse Embryonic Stem Cells , 2008, Cell.

[41]  W. Herr,et al.  HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation , 2012, Proceedings of the National Academy of Sciences.

[42]  D. Skalnik,et al.  CpG-binding Protein (CXXC Finger Protein 1) Is a Component of the Mammalian Set1 Histone H3-Lys4 Methyltransferase Complex, the Analogue of the Yeast Set1/COMPASS Complex* , 2005, Journal of Biological Chemistry.

[43]  T. Kristie,et al.  Control of alpha-herpesvirus IE gene expression by HCF-1 coupled chromatin modification activities. , 2010, Biochimica et biophysica acta.

[44]  J. Capone,et al.  Host Cell Factor-1 and E2F4 Interact Via Multiple Determinants in Each Protein , 2006, Molecular and Cellular Biochemistry.