I. Present, I. A. Chromatin, W. H4k20me3, . To, and . Heterochromatin, Coverage of either H3K36me3 (active chromatin) or H3K9me3 (silent chromatin) ChIP-seq reads was calculated at H4K20me1/ -me3 peak sites and plotted as boxplot. * indicates statistical significance with p-value < 0, FIGURE, vol.429, pp.4-20

O. Preferentially, Coverage of pre-RC components was calculated at either H4K20me1 or ? me3 sites, to get a first impression of a direct association of either histone modification with pre-RC. All pre-RC components Orc2, Orc3, Mcm3, and Mcm7 were not particularly enriched at H4K20me1 sites

H. Accordingly and T. Orc, Mcm2-7 and pre-RCs hardly overlapped with H4K20me1 (Appendix Figure 24

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A. Figure-pre-rc, . Binding, . Laminb2, . Is, . By-t-pic et al., Input: grey, Orc2: red, Orc3: orange, Mcm3: blue, Mcm7: turquois. T-PIC-detected peaks are visualized as bars; HOMER-detected peaks are additionally highlighted by lightblue background. Position of LaminB2 origin is marked by green horizontal line, pp.2416622-2440010

A. Figure-pre-rc, . Binding, . Junb, . Is, . By-t-pic et al., Input: grey, Orc2: red, Orc3: orange, Mcm3: blue, Mcm7: turquois. T-PIC-detected peaks are visualized as bars; HOMER-detected peaks are additionally highlighted by lightblue background. Position of JunB origin is marked by green horizontal line, pp.12882387-12904261

A. Figure and G. S. Vs, Left: HOMER-defined complexes, right: T-PICdefined complexes. Venn diagram of overlap between G1-and S/G2-defined complexes with H3K4me3 peaks, RIGHT PANEL) DEFINED ORC AND MCM2-7 WITH H3K4ME3 PEAKS IN

A. Figure, . Visualization, H. Orc, and . Colocalization, Input: grey, Orc2: red, Orc3: orange, Mcm3: blue, Mcm7: turquois, H4K20me3: violet, pp.18071736-18101785

A. To, . Induction, and . Conversion, ChIP-qPCR analysis at FR and UAS sequences of FR-UAS reporter plasmids transfected in the indicated cell lines

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M. , P. Origin, . Identified-by-t-pic, . But, H. By et al., 65 FIGURE 4 CORRELATION 67 FIGURE 4 A) MEAN 70 FIGURE 4, PRE-RC COMPONENT COVERAGE ANALYSIS REVEALED INCREASED COVERAGE AT ACTIVE TSS (LEFT PANEL) AND UNCHANGED COVERAGE AT INACTIVE TSS (RIGHT PANEL). A) MEAN ORC2 COVERAGE. B) MEAN ORC3 COVERAGE. C) MEAN MCM3 COVERAGE. D) MEAN MCM7 COVERAGE. 74 FIGURE 4G2) AT AS (LEFT PANEL) AND DS (RIGHT PANEL). A) MEAN MCM2-7 APPROXIMATED ORC IN S/G2. 90 FIGURE 4.29: H4K20ME1 IS PRESENT IN ACTIVE CHROMATIN, WHILE H4K20ME3 CORRESPONDS TO HETEROCHROMATIN. 95 FIGURE 4.30: COVERAGE OF PRE-RC COMPONENTS (G1) AT H4K20ME1 PEAKS. A) MEAN ORC2 COVERAGE. B) MEAN ORC3 COVERAGE. C) MEAN MCM3 COVERAGE. D) MEAN MCM7 COVERAGE. 96 FIGURE 4.31: ORC SHOWED INCREASED COVERAGE AT H4K20ME3 PEAKS. A) MEAN ORC2 COVERAGE. B) MEAN ORC3 COVERAGE. C) MEAN MCM3 COVERAGE. D) MEAN MCM7 COVERAGE. 97 FIGURE 4.32: MOSTLY HOMER-(LEFT) AND T-PIC-(RIGHT) DEFINED ORC OVERLAPPED WITH H4K20ME3. 98 FIGURE 4.33: SCHEMATIC REPRESENTATION OF EXPERIMENTAL SETUP. A) EBV-DERIVED AUTOSOMAL REPORTER PLASMID SYSTEM. B) PLASMID ABUNDANCE EXPERIMENTS. 101 FIGURE 4.34: GENERATION OF HEK293 EBNA1 + GAL4 (-FUSION) CELL LINES. 102 FIGURE 4 TARGETING TO FR-ORI RDH AND FR-UAS ORI RDH UNSPECIFICALLY INDUCES H4K20ME3 ALL OVER THE PLASMIDS. 103 FIGURE 4, pp.4-20

P. Plasmids, . Licensing, . Activation, . Defined, . In et al., 106 FIGURE 4, SUV4- 20H1 FLOX/-, SUV4-20H1 -/-MEFS, TREATED OR NOT WITH 4-OHT. B) RELATIVE SNS ENRICHMENT C) CHIP-QPCR ANALYSIS 108 FIGURE 4.41: IMMUNOBLOT CONFIRMATION OF A-196 COMPOUND INHIBITING H4K20ME2/3. 110 FIGURE 4.42: PR-SET7 TARGETING IN PRESENCE OF A-196 LED TO REDUCED H4K20ME3 LEVELS AND PRE-RC FORMATION COMPARED TO UNTREATED CELLS. 110 FIGURE 4.43: ENHANCED REPLICATION DURING PR-SET7 DEPENDS ON H4K20ME3. QUANTIFICATION OF FR-ORI RDH AND FR-UAS-ORI RDH PLASMIDS, p.111

A. Figure, . Representation, . The, I. Similarity, . Homer et al., 120 APPENDIX FIGURE 3: VALIDATION OF ES CELL PLURIPOTENCY. A) CELL MORPHOLOGY. B) FACS STAIN OF PLURIPOTENCY MARKERS OCT4 AND SSEA4, REPRESENTATIVE EXAMPLE ANALYSIS FOR A) ORC3 AND B) MCM7 IN ONE REPLICATE. 124 APPENDIX FIGURE 7: PRE-RC BINDING AT LAMINB2 ORIGIN IS DETECTED, p.125, 2012.

A. Figure-pre-rc, . Binding, . Junb, . Is, . By-t-pic et al., 126 APPENDIX FIGURE 9: ORC AND MCM2-7 COMPLEX SIZES A) ORC. B) MCM2-7. 127 APPENDIX FIGURE 10: OVERLAPS OF HOMER-AND T-PIC DEFINED COMPLEXES. A) ORC B) MCM2-7. 128 APPENDIX FIGURE 11, 129 APPENDIX FIGURE 12: GENOMIC DISTRIBUTION OF H3K4ME3 PEAKS SHOWED CLOSE ASSOCIATION TO REGULATORY 5' GENIC REGIONS. 130 APPENDIX FIGURE 13: H3K4ME3 POSITIONS WERE MORE LOCALIZED THAN H3K36ME3. 131 APPENDIX FIGURE 14: GENOMIC DISTRIBUTION OF H3K36ME3 PEAKS SHOWED ENRICHMENT IN INTRONS, p.132

A. Figure, . Coverage, . Pre-rc, . At, and . Peaks, NO, A) MEAN ORC2 COVERAGE. B) MEAN ORC3 COVERAGE. C) MEAN MCM3 COVERAGE. D) MEAN MCM7 COVERAGE

A. Figure, H. Orc, A. Mcm2-7, . Pre-rc, . Were et al., 135 APPENDIX FIGURE 18: COMPARISON C) T-PIC-DEFINED MCM2-7 DENSITIES. 136 APPENDIX FIGURE 137 APPENDIX FIGURE 20: OVERLAPS OF HOMER-(LEFT PANEL), 140 APPENDIX FIGURE 23: H4K20ME1 AND ?ME3 POSITIONS ARE MUTUALLY EXCLUSIVE. A) H4K20ME1 AND ?ME3 PEAK SIZES REPRESENTED IN A BOXLOT. B) OVERLAP OF H4K20ME1 AND ?ME3 PEAK POSITIONS. 141 APPENDIX FIGURE 24: HOMER-(LEFT PANEL) AND T-PIC-(RIGHT PANEL) DEFINED COMPLEXES HARDLY OVERLAP WITH H4K20ME1. 142 APPENDIX FIGURE 25: IGB VISUALIZATION OF ORC AND H4K20ME3 COLOCALIZATION. 143 APPENDIX FIGURE 26: COMPARISON OF H4K20ME1 AND ?ME3 POSITIONS IN G1 AND S/G2. A) H4K20ME1. B) H4K20ME3. 144 APPENDIX FIGURE 27: H4K20ME1 AND ?ME3 COVERAGE AT H4K20ME1 AND ?ME 3 PEAKS (G1 VS. S/G2). 145 APPENDIX FIGURE TARGETING HAS NO EFFECT ON PLASMID REPLICATION. QUANTIFICATION OF FR-ORI RDH AND FR-UAS-ORI RDH PLASMIDS. 146 APPENDIX FIGURE 29: DIRECT COMPARISON OF ALL REPORTER PLASMID REPLICATION EFFICIENCIES RELATIVE TO FR-DS. 147 APPENDIX FIGURE 30: PR-SET7 TARGETING TO FR-UAS LED TO H4K20ME1 INDUCTION AND CONVERSION INTO H4K20ME3, pp.4-20