Table 1. Summary of origin features... | Rockefeller University Press

Table 1.

Summary of origin features reported in mammalian genome-wide mapping studies

Study	Origin purification	Detection	Genome span	Cell type	Origin number	Mean origin spacing	Mean origin size	Main origin features
			Mb			kb	kb
Human
Lucas et al., 2007	SSS	Microarray	1,425	11365	32	<50	<5	80% within transcription units. Correlated with chromatin acetylation.
Cadoret et al., 2008	λ-SNS	Microarray	30 (ENCODE)	HeLa	283	63	<5	Clustered in GC-rich regions. Rare in GC-poor regions. Associated with CGI, TRE, and c-JUN and c-FOS BSs, with open chromatin due to CGIs, with DNase HSSs and with evolutionarily conserved regions.
Karnani et al., 2010	λ-SNS/BrdU-SNS	Microarray	30 (ENCODE)	HeLa	150	58/28	1.4/1.7	AT-rich but within GC-rich regions, associated with conserved evolutionary elements. λ-SNS and λ-SNS + BrdU SNS intersects enriched in TSSs, but BrdU-SNS specific peaks depleted in TSSs.
Mesner et al., 2011	Bubble trap	Microarray	30 (ENCODE)	Early S HeLa/HeLa/GM06990	111 (646)/128 (657)/177 (988)	58/69/41	15.2/18.1/14.5	Broad initiation zones covering 15–22% of the genome, within intergenic regions as well as within or overlapping active and inactive genes. 20% encompass 5′ end of or entire active genes and activating histone marks. Overlap by only ∼1/3 between cell types and affected by synchronization.
Valenzuela et al., 2011	SSS, λ-SNS/λ-SNS	Microarray sequencing	34/3,000 (WG)	MCF-7, BT474, H520/MCF-7	8,281	4	NR	>70% conserved in all cell lines. Enriched at active TSSs and in H3K4me3 and Pol-II. Associated with conserved evolutionary elements.
Martin et al., 2011	λ-SNS	Sequencing	3,000 (WG)	K562, MCF-7	NR	NR	NR	Clustered near regions of moderate transcription. Rare in highly transcribed or nontranscribed regions. Excluded from TSSs but enriched ∼0.5 kb downstream. Strongly associated with meCpGs and DNase HSSs./Weakly associated with umCpGs, miRNA transcripts, CTCF, Pol-II and c-JUN BSs, H3K4 me, H3K29ac, and H3K27ac.
Besnard et al., 2012	λ-SNS	Sequencing	3,000 (WG)	HeLa, IMR-90, hESC H9, iPSCs from IMR-90	250,000	11	0.5	Often grouped in clusters (mean size of 11 kb). At saturation cover ∼10% of the genome. One half within genes, <18% with TSS and CGI. 65–84% pairwise overlap between cell lines, few and inefficient cell type–specific origins. Density correlated with percentage of GC, timing, and efficiency. 91% associated with G4. Strand asymmetric distribution of G, C, and G4.
Mesner et al., 2013	Bubble trap	Sequencing	3,000 (WG)	GM06990	72,812 (123,297)	NR	20	Broad initiation zones covering 24% of the genome. 17,999 early, 25,735 mid-, and 29,020 late-replicating zone of mean size 27 kb, 18 kb, and 16 kb./Early zones more focused and efficient than late zones. Majority in nontranscribed DNA regardless of firing time. Early but not mid- and late zones associated with transcribed genes and activating marks DNase I HSSs (58%), H3K4me3, H3K27me3, H3K36me3, and CTCF BSs. At megabase scale, late zones anticorrelated with both activating and repressive marks. Densities were highest in both highly accessible and highly compact chromatin.
Dellino et al., 2013	ORC1-ChIP	Sequencing	3,000 (WG)	HeLa	13,600	NR	NR	Mostly associated with TSSs of coding and noncoding RNAs. 39% of all expressed TSSs in HeLa cells. Most and least transcribed sites associated with coding and noncoding RNAs, respectively. No consensus sequence.
Picard et al., 2014	λ-SNS	Sequencing	3,000 (WG)	K562	59,185	NR	3.4	Reanalyzed data of Besnard et al. (2012) and found 80,000–90,000 origins for each cell type. Early origins shared between cell types. Cell type–specific origins replicate late. 80% of CGI-associated origins are constitutive. 76% of CGIs are origins. Efficiency correlated with H4K20me1 + H3K27me3.
Mukhopadhyay et al., 2014	λ-SNS/BrdU-SNS	Sequencing	3,000 (WG)	Primary basophilic erythroblasts	100,000	NR	NR	Association with G4 (37%), CGIs (7%), and TSSs (13%). DNase I HSSs associated with but not required for origin formation.
Mouse
Sequeira-Mendes et al., 2009	λ-SNS	Microarray	10.1	mESC PGK12, MEFs, NIH-3T3	97	103	NR	Most within transcription units. Half at CGI promoters. Efficiency conserved across cell types and correlated with embryonic TSSs.
Cayrou et al., 2011	λ-SNS	Microarray	60.4/118.3	mESC GCR8, mTC P19, MEFs/Kc (Drosophila)	2,748/6,184	21/19	NR	44% conserved between cell types. Spacing fivefold smaller than IOD on combed DNA. Inferred firing efficiency 20%. Preferentially intragenic./Bimodal distribution of SNS around CGI. G-rich motifs and local nucleotide skew./Drosophila origins correlated with HP1 BSs.

Study	Origin purification	Detection	Genome span	Cell type	Origin number	Mean origin spacing	Mean origin size	Main origin features
			Mb			kb	kb
Human
Lucas et al., 2007	SSS	Microarray	1,425	11365	32	<50	<5	80% within transcription units. Correlated with chromatin acetylation.
Cadoret et al., 2008	λ-SNS	Microarray	30 (ENCODE)	HeLa	283	63	<5	Clustered in GC-rich regions. Rare in GC-poor regions. Associated with CGI, TRE, and c-JUN and c-FOS BSs, with open chromatin due to CGIs, with DNase HSSs and with evolutionarily conserved regions.
Karnani et al., 2010	λ-SNS/BrdU-SNS	Microarray	30 (ENCODE)	HeLa	150	58/28	1.4/1.7	AT-rich but within GC-rich regions, associated with conserved evolutionary elements. λ-SNS and λ-SNS + BrdU SNS intersects enriched in TSSs, but BrdU-SNS specific peaks depleted in TSSs.
Mesner et al., 2011	Bubble trap	Microarray	30 (ENCODE)	Early S HeLa/HeLa/GM06990	111 (646)/128 (657)/177 (988)	58/69/41	15.2/18.1/14.5	Broad initiation zones covering 15–22% of the genome, within intergenic regions as well as within or overlapping active and inactive genes. 20% encompass 5′ end of or entire active genes and activating histone marks. Overlap by only ∼1/3 between cell types and affected by synchronization.
Valenzuela et al., 2011	SSS, λ-SNS/λ-SNS	Microarray sequencing	34/3,000 (WG)	MCF-7, BT474, H520/MCF-7	8,281	4	NR	>70% conserved in all cell lines. Enriched at active TSSs and in H3K4me3 and Pol-II. Associated with conserved evolutionary elements.
Martin et al., 2011	λ-SNS	Sequencing	3,000 (WG)	K562, MCF-7	NR	NR	NR	Clustered near regions of moderate transcription. Rare in highly transcribed or nontranscribed regions. Excluded from TSSs but enriched ∼0.5 kb downstream. Strongly associated with meCpGs and DNase HSSs./Weakly associated with umCpGs, miRNA transcripts, CTCF, Pol-II and c-JUN BSs, H3K4 me, H3K29ac, and H3K27ac.
Besnard et al., 2012	λ-SNS	Sequencing	3,000 (WG)	HeLa, IMR-90, hESC H9, iPSCs from IMR-90	250,000	11	0.5	Often grouped in clusters (mean size of 11 kb). At saturation cover ∼10% of the genome. One half within genes, <18% with TSS and CGI. 65–84% pairwise overlap between cell lines, few and inefficient cell type–specific origins. Density correlated with percentage of GC, timing, and efficiency. 91% associated with G4. Strand asymmetric distribution of G, C, and G4.
Mesner et al., 2013	Bubble trap	Sequencing	3,000 (WG)	GM06990	72,812 (123,297)	NR	20	Broad initiation zones covering 24% of the genome. 17,999 early, 25,735 mid-, and 29,020 late-replicating zone of mean size 27 kb, 18 kb, and 16 kb./Early zones more focused and efficient than late zones. Majority in nontranscribed DNA regardless of firing time. Early but not mid- and late zones associated with transcribed genes and activating marks DNase I HSSs (58%), H3K4me3, H3K27me3, H3K36me3, and CTCF BSs. At megabase scale, late zones anticorrelated with both activating and repressive marks. Densities were highest in both highly accessible and highly compact chromatin.
Dellino et al., 2013	ORC1-ChIP	Sequencing	3,000 (WG)	HeLa	13,600	NR	NR	Mostly associated with TSSs of coding and noncoding RNAs. 39% of all expressed TSSs in HeLa cells. Most and least transcribed sites associated with coding and noncoding RNAs, respectively. No consensus sequence.
Picard et al., 2014	λ-SNS	Sequencing	3,000 (WG)	K562	59,185	NR	3.4	Reanalyzed data of Besnard et al. (2012) and found 80,000–90,000 origins for each cell type. Early origins shared between cell types. Cell type–specific origins replicate late. 80% of CGI-associated origins are constitutive. 76% of CGIs are origins. Efficiency correlated with H4K20me1 + H3K27me3.
Mukhopadhyay et al., 2014	λ-SNS/BrdU-SNS	Sequencing	3,000 (WG)	Primary basophilic erythroblasts	100,000	NR	NR	Association with G4 (37%), CGIs (7%), and TSSs (13%). DNase I HSSs associated with but not required for origin formation.
Mouse
Sequeira-Mendes et al., 2009	λ-SNS	Microarray	10.1	mESC PGK12, MEFs, NIH-3T3	97	103	NR	Most within transcription units. Half at CGI promoters. Efficiency conserved across cell types and correlated with embryonic TSSs.
Cayrou et al., 2011	λ-SNS	Microarray	60.4/118.3	mESC GCR8, mTC P19, MEFs/Kc (Drosophila)	2,748/6,184	21/19	NR	44% conserved between cell types. Spacing fivefold smaller than IOD on combed DNA. Inferred firing efficiency 20%. Preferentially intragenic./Bimodal distribution of SNS around CGI. G-rich motifs and local nucleotide skew./Drosophila origins correlated with HP1 BSs.

WG, whole genome; NR, not reported; iPSCs, induced pluripotent stem cells; mESC, mouse embryonic stem cell; hESC, human embryonic stem cell; MEFs, mouse embryonic fibroblasts; mTC, mouse teratocarcinoma; CGI, CpG islands; TRE, transcriptional regulatory elements; ChIP, chromatin immunoprecipitation; HSS, hypersensitive site; CTCF, CCCTC-binding factor; Pol II, RNA polymerase II; meCpG, methylated CpG dinucleotide; umCpG, unmethylated CpG; G4, G-quadruplex elements; BS, binding site; IOD, inter-origin distance; HP1, heterochromatin protein 1; For Mesner et al. (2011, 2013), the numbers in parentheses indicate the number of individual EcoRI fragments clustering into the indicated number of initiation zones.

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