LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome

Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns.

[1]  E. Lewis.  A gene complex controlling segmentation in Drosophila , 1978, Nature.

[2]  E. Meyerowitz,et al.  A Polycomb-group gene regulates homeotic gene expression in Arabidopsis , 1997, Nature.

[3]  L. Sieburth,et al.  Molecular dissection of the AGAMOUS control region shows that cis elements for spatial regulation are located intragenically. , 1997, The Plant cell.

[4]  Marilu A. Hoeppner,et al.  Maternal control of embryogenesis by MEDEA, a polycomb group gene in Arabidopsis. , 1998, Science.

[5]  R. DePinho,et al.  The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus , 1999, Nature.

[6]  Z. R. Sung,et al.  EMBRYONIC FLOWER2, a Novel Polycomb Group Protein Homolog, Mediates Shoot Development and Flowering in Arabidopsis Article, publication date, and citation information can be found at www.aspb.org/cgi/doi/10.1105/tpc.010227. , 2001, The Plant Cell Online.

[7]  V. Gaudin,et al.  Mutations in LIKE HETEROCHROMATIN PROTEIN 1 affect flowering time and plant architecture in Arabidopsis. , 2001, Development.

[8]  Allison K. Wilson,et al.  The VERNALIZATION 2 Gene Mediates the Epigenetic Regulation of Vernalization in Arabidopsis , 2001, Cell.

[9]  W. Peacock,et al.  Different Regulatory Regions Are Required for the Vernalization-Induced Repression of FLOWERING LOCUS C and for the Epigenetic Maintenance of Repression Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.004564. , 2002, The Plant Cell Online.

[10]  L. Hennig,et al.  The Polycomb-group protein MEDEA regulates seed development by controlling expression of the MADS-box gene PHERES1. , 2003, Genes & development.

[11]  D. Beach,et al.  Polycomb CBX7 has a unifying role in cellular lifespan , 2004, Nature Cell Biology.

[12]  Christine Stock,et al.  Interaction of Polycomb-group proteins controlling flowering in Arabidopsis , 2004, Development.

[13]  K. Nakahigashi,et al.  The Arabidopsis heterochromatin protein1 homolog (TERMINAL FLOWER2) silences genes within the euchromatic region but not genes positioned in heterochromatin. , 2005, Plant & cell physiology.

[14]  Berend Snijder,et al.  The Arabidopsis LHP1 protein is a component of euchromatin , 2005, Planta.

[15]  Vincent Colot,et al.  Profiling histone modification patterns in plants using genomic tiling microarrays , 2005, Nature Methods.

[16]  B. Steensel,et al.  Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster , 2006, Nature Genetics.

[17]  Megan F. Cole,et al.  Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells , 2006, Cell.

[18]  Kristian Helin,et al.  Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. , 2006, Genes & development.

[19]  T. Jenuwein,et al.  Silencing by plant Polycomb‐group genes requires dispersed trimethylation of histone H3 at lysine 27 , 2006, The EMBO journal.

[20]  U. Grossniklaus,et al.  Different Polycomb group complexes regulate common target genes in Arabidopsis , 2006, EMBO reports.

[21]  J. Micol,et al.  INCURVATA2 Encodes the Catalytic Subunit of DNA Polymerase α and Interacts with Genes Involved in Chromatin-Mediated Cellular Memory in Arabidopsis thaliana , 2007, The Plant Cell Online.

[22]  Vincent Colot,et al.  Arabidopsis TFL2/LHP1 Specifically Associates with Genes Marked by Trimethylation of Histone H3 Lysine 27 , 2007, PLoS genetics.

[23]  V. Gaudin,et al.  The Arabidopsis LHP1 protein colocalizes with histone H3 Lys27 trimethylation , 2007, Nature Structural &Molecular Biology.

[24]  M. Begemann,et al.  Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective , 2007, Stem cells.

[25]  Danhua Jiang,et al.  Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb Repressive Complex 2 Components , 2008, PloS one.

[26]  Z. R. Sung,et al.  EMBRYONIC FLOWER1 Participates in Polycomb Group–Mediated AG Gene Silencing in Arabidopsis[W] , 2008, The Plant Cell Online.

[27]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[28]  Alexandra M. E. Jones,et al.  A PHD-Polycomb Repressive Complex 2 triggers the epigenetic silencing of FLC during vernalization , 2008, Proceedings of the National Academy of Sciences.

[29]  Polycomb silencing of KNOX genes confines shoot stem cell niches in Arabidopsis. , 2008, Current biology : CB.

[30]  Antoine H. F. M. Peters,et al.  Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. , 2008, Developmental cell.

[31]  Simon Kasif,et al.  Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains , 2008, PLoS genetics.

[32]  Sookyung Oh,et al.  Genic and Global Functions for Paf1C in Chromatin Modification and Gene Expression in Arabidopsis , 2008, PLoS genetics.

[33]  L. Hennig,et al.  The Chromodomain of LIKE HETEROCHROMATIN PROTEIN 1 Is Essential for H3K27me3 Binding and Function during Arabidopsis Development , 2009, PloS one.

[34]  Chen Zeng,et al.  A clustering approach for identification of enriched domains from histone modification ChIP-Seq data , 2009, Bioinform..

[35]  X. Liu,et al.  Genome-Wide and Organ-Specific Landscapes of Epigenetic Modifications and Their Relationships to mRNA and Small RNA Transcriptomes in Maize[W] , 2009, The Plant Cell Online.

[36]  Lior Pachter,et al.  Sequence Analysis , 2020, Definitions.

[37]  Lisha Shen,et al.  Regulation of floral patterning by flowering time genes. , 2009, Developmental cell.

[38]  Laura Fanti,et al.  Heterochromatin Protein 1 (HP1a) Positively Regulates Euchromatic Gene Expression through RNA Transcript Association and Interaction with hnRNPs in Drosophila , 2009, PLoS genetics.

[39]  T. Zhu,et al.  Epigenetic Regulation of Gene Programs by EMF1 and EMF2 in Arabidopsis1[W][OA] , 2009, Plant Physiology.

[40]  E. Finnegan,et al.  Mechanisms of gene repression by vernalization in Arabidopsis. , 2009, The Plant journal : for cell and molecular biology.

[41]  Cole Trapnell,et al.  Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. , 2010, Nature biotechnology.

[42]  M. Koch,et al.  Keeping Cell Identity in Arabidopsis Requires PRC1 RING-Finger Homologs that Catalyze H2A Monoubiquitination , 2010, Current Biology.

[43]  C. Glass,et al.  Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. , 2010, Molecular cell.

[44]  Y. Qi,et al.  Global Epigenetic and Transcriptional Trends among Two Rice Subspecies and Their Reciprocal Hybrids[W] , 2010, Plant Cell.

[45]  W. Shen,et al.  The Arabidopsis PRC1-like ring-finger proteins are necessary for repression of embryonic traits during vegetative growth , 2010, Cell Research.

[46]  J. A. Jarillo,et al.  EARLY IN SHORT DAYS 7 (ESD7) encodes the catalytic subunit of DNA polymerase epsilon and is required for flowering repression through a mechanism involving epigenetic gene silencing. , 2010, The Plant journal : for cell and molecular biology.

[47]  S. Raguz,et al.  Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. , 2010, Molecular cell.

[48]  L. Hennig,et al.  H3K27me3 Profiling of the Endosperm Implies Exclusion of Polycomb Group Protein Targeting by DNA Methylation , 2010, PLoS genetics.

[49]  Ming-Ming Zhou,et al.  Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression. , 2011, Cancer research.

[50]  K. Ljung,et al.  TFL2/LHP1 is involved in auxin biosynthesis through positive regulation of YUCCA genes. , 2011, The Plant journal : for cell and molecular biology.

[51]  Ming-Ming Zhou,et al.  Long Noncoding RNA , Polycomb , and the Ghosts Haunting INK 4 bARF-INK 4 a Expression , 2011 .

[52]  Nathalie Simoncello,et al.  Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1 , 2011, PloS one.

[53]  M. Rehmsmeier,et al.  High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Arabidopsis Endosperm , 2011, PLoS genetics.

[54]  A. Rechtsteiner,et al.  Broad chromosomal domains of histone modification patterns in C. elegans. , 2011, Genome research.

[55]  A. Wutz.  Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation , 2011, Nature Reviews Genetics.

[56]  O. Clarenz,et al.  Dynamic Regulation of H3K27 Trimethylation during Arabidopsis Differentiation , 2011, PLoS genetics.

[57]  D. Buzas,et al.  Vernalization-Repression of Arabidopsis FLC Requires Promoter Sequences but Not Antisense Transcripts , 2011, PloS one.

[58]  S. Luan,et al.  The cyclophilin AtCYP71 interacts with CAF-1 and LHP1 and functions in multiple chromatin remodeling processes. , 2011, Molecular plant.

[59]  Benjamin Leblanc,et al.  Polycomb-Dependent Regulatory Contacts between Distant Hox Loci in Drosophila , 2011, Cell.

[60]  Sibum Sung,et al.  Vernalization-Mediated Epigenetic Silencing by a Long Intronic Noncoding RNA , 2011, Science.

[61]  Arp Schnittger,et al.  Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition , 2011, PLoS genetics.

[62]  L. Lepiniec,et al.  Transcriptional Regulation of Arabidopsis LEAFY COTYLEDON2 Involves RLE, a cis-Element That Regulates Trimethylation of Histone H3 at Lysine-27[W] , 2011, Plant Cell.

[63]  A. Bauer,et al.  Histone methylation by PRC2 is inhibited by active chromatin marks. , 2011, Molecular cell.

[64]  A. Tanay,et al.  Three-Dimensional Folding and Functional Organization Principles of the Drosophila Genome , 2012, Cell.

[65]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[66]  D. Zilberman,et al.  EMF1 and PRC2 Cooperate to Repress Key Regulators of Arabidopsis Development , 2012, PLoS genetics.

[67]  Giacomo Cavalli,et al.  Polycomb: a paradigm for genome organization from one to three dimensions. , 2012, Current opinion in cell biology.

[68]  J. C. del Pozo,et al.  Regulation of the new Arabidopsis imprinted gene AtBMI1C requires the interplay of different epigenetic mechanisms. , 2012, Molecular plant.

[69]  S. Jacobsen,et al.  Loss of the DNA Methyltransferase MET1 Induces H3K9 Hypermethylation at PcG Target Genes and Redistribution of H3K27 Trimethylation to Transposons in Arabidopsis thaliana , 2012, PLoS genetics.

[70]  K. Helin,et al.  Transcriptional regulation by Polycomb group proteins , 2013, Nature Structural &Molecular Biology.

[71]  Matteo Pellegrini,et al.  Long-range chromatin contacts in embryonic stem cells reveal a role for pluripotency factors and polycomb proteins in genome organization. , 2013, Cell stem cell.

[72]  Y. Schwartz,et al.  A new world of Polycombs: unexpected partnerships and emerging functions , 2013, Nature Reviews Genetics.

[73]  E. Nestler,et al.  diffReps: Detecting Differential Chromatin Modification Sites from ChIP-seq Data with Biological Replicates , 2013, PloS one.

[74]  Nathan M. Springer,et al.  Genomic Distribution of Maize Facultative Heterochromatin Marked by Trimethylation of H3K27[W] , 2013, Plant Cell.

[75]  F. Turck,et al.  VAL- and AtBMI1-Mediated H2Aub Initiate the Switch from Embryonic to Postgerminative Growth in Arabidopsis , 2013, Current Biology.

[76]  M. Timmermans,et al.  The ASYMMETRIC LEAVES complex maintains repression of KNOX homeobox genes via direct recruitment of Polycomb-repressive complex2. , 2013, Genes & development.

[77]  L. Hennig,et al.  Arabidopsis MSI1 connects LHP1 to PRC2 complexes , 2013, The EMBO journal.

[78]  Hua Ying,et al.  Arabidopsis Polycomb Repressive Complex 2 binding sites contain putative GAGA factor binding motifs within coding regions of genes , 2013, BMC Genomics.

[79]  B. Bernstein,et al.  SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing. , 2013, Developmental cell.

[80]  Sibum Sung,et al.  The catalytic subunit of Arabidopsis DNA polymerase α ensures stable maintenance of histone modification , 2013, Development.

[81]  Matteo Pellegrini,et al.  Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution chromatin interactions in Arabidopsis. , 2014, Molecular cell.

[82]  F. Ariel,et al.  The BAF60 Subunit of the SWI/SNF Chromatin-Remodeling Complex Directly Controls the Formation of a Gene Loop at FLOWERING LOCUS C in Arabidopsis[W] , 2014, Plant Cell.

[83]  Eric Nestler,et al.  ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases , 2014, BMC Genomics.

[84]  Teddy Jégu,et al.  Noncoding transcription by alternative RNA polymerases dynamically regulates an auxin-driven chromatin loop. , 2014, Molecular cell.

[85]  Marc W. Schmid,et al.  Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco locus of Drosophila. , 2014, Molecular cell.

[86]  David J. Arenillas,et al.  JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles , 2013, Nucleic Acids Res..

[87]  Y. Schwartz,et al.  Ruled by ubiquitylation: a new order for polycomb recruitment. , 2014, Cell reports.

[88]  L. Hennig,et al.  Variations on a theme: Polycomb group proteins in plants. , 2014, Journal of experimental botany.

[89]  Joana Sequeira-Mendes,et al.  The Functional Topography of the Arabidopsis Genome Is Organized in a Reduced Number of Linear Motifs of Chromatin States[C][W] , 2014, Plant Cell.

[90]  Robert J. Schmitz,et al.  Photoperiodic control of the floral transition through a distinct polycomb repressive complex. , 2014, Developmental cell.

[91]  Y. Gan,et al.  The putative PRC1 RING-finger protein AtRING1A regulates flowering through repressing MADS AFFECTING FLOWERING genes in Arabidopsis , 2014, Development.

[92]  Louise S. Matheson,et al.  Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome , 2015, Nature Genetics.

[93]  L. Hennig,et al.  The polycomb group protein regulatory network. , 2015, Annual review of plant biology.

[94]  Teddy Jégu,et al.  Battles and hijacks: noncoding transcription in plants. , 2015, Trends in plant science.

[95]  Philip A. Ewels,et al.  HiCUP: pipeline for mapping and processing Hi-C data , 2015, F1000Research.