DNA Replication Timing Is Maintained Genome-Wide in Primary Human Myoblasts Independent of D4Z4 Contraction in FSH Muscular Dystrophy
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{"title"=>"DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy", "type"=>"journal", "authors"=>[{"first_name"=>"Benjamin D.", "last_name"=>"Pope", "scopus_author_id"=>"36126828700"}, {"first_name"=>"Koji", "last_name"=>"Tsumagari", "scopus_author_id"=>"8859037700"}, {"first_name"=>"Dana", "last_name"=>"Battaglia", "scopus_author_id"=>"52463182700"}, {"first_name"=>"Tyrone", "last_name"=>"Ryba", "scopus_author_id"=>"25628701500"}, {"first_name"=>"Ichiro", "last_name"=>"Hiratani", "scopus_author_id"=>"6505888438"}, {"first_name"=>"Melanie", "last_name"=>"Ehrlich", "scopus_author_id"=>"7102895420"}, {"first_name"=>"David M.", "last_name"=>"Gilbert", "scopus_author_id"=>"7401956034"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"22096571", "pui"=>"362904776", "scopus"=>"2-s2.0-80855157444", "doi"=>"10.1371/journal.pone.0027413", "isbn"=>"1932-6203", "sgr"=>"80855157444"}, "id"=>"7ecb859b-54c1-351f-ae43-533ba96535a9", "abstract"=>"Facioscapulohumeral muscular dystrophy (FSHD) is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.", "link"=>"http://www.mendeley.com/research/dna-replication-timing-maintained-genomewide-primary-human-myoblasts-independent-d4z4-contraction-fs", "reader_count"=>21, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Master"=>1, "Other"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Master"=>1, "Other"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/713459"], "description"=>"<p>Step 1 illustrates BrdU labeling of actively dividing cells for 2 hours, followed by fixation and FACS sorting by DNA content into early and late S phase fractions. In step 2, BrdU-labeled DNA from each fraction was isolated by immunoprecipitation. Step 3 involved differential-labeling and co-hybridization to a whole-genome human CGH microarray. For the final step, arrays were scanned and the extracted log<sub>2</sub>(early/late) raw data was Loess normalized (represented by gray data points) and then smoothed (dark blue curve) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027413#pone.0027413-Ryba2\" target=\"_blank\">[35]</a>. Shown is a profile of approximately 60 Mb of chromosome 10 for patient CM1.</p>", "links"=>[], "tags"=>["genome-wide", "replication", "profiles"], "article_id"=>383816, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Method_for_generation_of_genome_wide_replication_profiles_of_primary_myoblasts_/383816", "title"=>"Method for generation of genome-wide replication profiles of primary myoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:03:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/714207"], "description"=>"<p>Primary human myoblast replication timing profiles are shown for 2 female (green) and 5 male (blue) individuals across the DXZ4 locus on chromosome X. Profiles for male lymphoblastoid (pink) and female fetal lung fibroblast (black) cell lines are also shown. Gaps in each profile represent regions between microarray probes. The purple box on the x-axis marks the position of DXZ4.</p>", "links"=>[], "tags"=>["containing", "dxz4", "replicates", "inactive"], "article_id"=>384565, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g006", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_region_containing_DXZ4_replicates_early_on_the_inactive_X_chromosome_/384565", "title"=>"The region containing DXZ4 replicates early on the inactive X chromosome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:16:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/361505"], "description"=>"<div><p>Facioscapulohumeral muscular dystrophy (FSHD) is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.</p> </div>", "links"=>[], "tags"=>["dna", "replication", "maintained", "genome-wide", "myoblasts", "d4z4", "contraction", "fsh", "muscular", "dystrophy"], "article_id"=>131462, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413", "stats"=>{"downloads"=>5, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/DNA_Replication_Timing_Is_Maintained_Genome_Wide_in_Primary_Human_Myoblasts_Independent_of_D4Z4_Contraction_in_FSH_Muscular_Dystrophy/131462", "title"=>"DNA Replication Timing Is Maintained Genome-Wide in Primary Human Myoblasts Independent of D4Z4 Contraction in FSH Muscular Dystrophy", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-11-11 00:24:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/713758"], "description"=>"<p>(A) Primary human myoblast replication timing profiles are shown for 3 control (gray) individuals and 4 FSHD (red) patients across the proximal region to 4q35. One FSHD dataset (FM7) had a low signal to noise ratio and deviates somewhat from other datasets, but was still included for comparison. (B) Replication timing profiles for many different human cell types are shown across the proximal region to 4q35. Boxed in red is the region of human chromosome 4 corresponding to 4q35. Microarray probe positions are indicated along the X-axis by short black vertical lines. Genes are indicated by black dots, for those whose name is given, or gray dots, for those with too high a density to add a label. <i>DUX4</i> transcripts derived from 4q35.2 D4Z4 map between hg18 chromosome 4 coordinates 191,229,361 and 191,247,457 (UCSC Genome Browser, <a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>).</p>", "links"=>[], "tags"=>["contraction", "fshd", "4q35", "replication"], "article_id"=>384116, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_D4Z4_contraction_and_FSHD_disease_background_do_not_affect_4q35_replication_timing_/384116", "title"=>"D4Z4 contraction and FSHD disease background do not affect 4q35 replication timing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:08:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/713886"], "description"=>"<p>(A) Primary human myoblast replication timing profiles are shown for 3 control (gray) individuals and 4 FSHD (red) patients across the proximal region to 10q26. One FSHD dataset (FM7) had a low signal to noise ratio and deviates somewhat from other datasets, but was still included for comparison. (B) Replication timing profiles for many different human cell types are shown across the proximal region to 10q26. Boxed in red is the region of human chromosome 10 corresponding to 10q26. Microarray probe positions are indicated along the X-axis by short black vertical lines. Genes are indicated by black dots, for those whose name is given, or gray dots, for those with too high a density to add a label. DUX4 transcripts derived from 10q26.3 D4Z4 map between hg18 chromosome 10 coordinates 135,330,358 and 135,338,574 (UCSC Genome Browser, <a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>).</p>", "links"=>[], "tags"=>["contraction", "fshd", "10q26", "replication"], "article_id"=>384241, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_D4Z4_contraction_and_FSHD_disease_background_do_not_affect_10q26_replication_timing_/384241", "title"=>"D4Z4 contraction and FSHD disease background do not affect 10q26 replication timing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:10:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/713590"], "description"=>"<p>(A) Genome-wide Pearson's correlations between individual control (begins with “C”) and FSHD (begins with “F”) primary myoblast timing profiles are displayed. Gray indicates control to control or FSHD to FSHD comparison. One FSHD dataset (FM7) had a low signal to noise ratio and deviates somewhat from other datasets, but was still included for comparison. (B) Genome-wide Pearson's correlations between averaged control and FSHD myoblasts as well as other human cell types are displayed. Gray indicates control to FSHD myoblast comparison.</p>", "links"=>[], "tags"=>["fshd", "myoblast", "genome-wide", "replication", "profiles"], "article_id"=>383944, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Similarity_between_FSHD_and_control_myoblast_genome_wide_replication_timing_profiles_and_other_cell_types_/383944", "title"=>"Similarity between FSHD and control myoblast genome-wide replication timing profiles and other cell types.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:05:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/714032"], "description"=>"<p>(A, B, C) Primary human myoblast replication timing profiles are shown for 3 control (gray) individuals and 4 FSHD (red) patients across the top three 200 kb regions (on chromosomes 5, 11, and X respectively) of greatest difference as identified using a distance-maximizing statistical method <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027413#pone.0027413-Ryba3\" target=\"_blank\">[39]</a>. Each 200 kb region of greatest difference between FSHD and control myoblasts is flanked by dashed, blue lines. Green arrows in panel C mark regions with gender-dependent differences caused by X-chromosome inactivation. The two lower curves in these regions are from the two female-derived myoblast samples and the other curves are myoblasts from males.</p>", "links"=>[], "tags"=>["fshd", "myoblast", "replication"], "article_id"=>384385, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regions_of_greatest_statistical_difference_between_control_and_FSHD_myoblast_replication_timing_profiles_/384385", "title"=>"Regions of greatest statistical difference between control and FSHD myoblast replication timing profiles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-11 01:13:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/714314"], "description"=>"<p>Myoblast culture source information.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "physiology", "cell biology"], "article_id"=>384671, "categories"=>["Physiology", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Benjamin D. Pope", "Koji Tsumagari", "Dana Battaglia", "Tyrone Ryba", "Ichiro Hiratani", "Melanie Ehrlich", "David M. Gilbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027413.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Myoblast_culture_source_information_/384671", "title"=>"Myoblast culture source information.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-11-11 01:17:51"}

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Relative Metric

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