Verfügbarkeit: DNA methylation dynamics in murine ageing and longevity

Gespeichert in:

Bibliographische Detailangaben
Beteilige Person:	Hahn, Oliver (VerfasserIn)
Format:	Hochschulschrift/Dissertation Buch
Sprache:	Englisch
Veröffentlicht:	Köln 2018
Schlagwörter:	Hochschulschrift
Links:	http://d-nb.info/1169447325/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030932055&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
Umfang:	XI, 144 Seiten Illustrationen 21 cm

Internformat

MARC


LEADER	00000nam a2200000 c 4500
001	BV045548028
003	DE-604
005	00000000000000.0
007	t\|
008	190408s2018 gw a\|\|\| m\|\|\| 00\|\|\| eng d
015			\|a 19,H01 \|2 dnb
016	7		\|a 1169447325 \|2 DE-101
020			\|c Broschur
035			\|a (OCoLC)1135396699
035			\|a (DE-599)DNB1169447325
040			\|a DE-604 \|b ger \|e rda
041	0		\|a eng
044			\|a gw \|c XA-DE
049			\|a DE-355 \|a DE-83
084			\|a 570 \|2 sdnb
084			\|a 610 \|2 sdnb
100	1		\|a Hahn, Oliver \|e Verfasser \|0 (DE-588)1172226512 \|4 aut
245	1	0	\|a DNA methylation dynamics in murine ageing and longevity \|c vorgelegt von Oliver Hahn
264		1	\|a Köln \|c 2018
300			\|a XI, 144 Seiten \|b Illustrationen \|c 21 cm
336			\|b txt \|2 rdacontent
337			\|b n \|2 rdamedia
338			\|b nc \|2 rdacarrier
502			\|b Dissertation \|c Universität zu Köln \|d 2018
655		7	\|0 (DE-588)4113937-9 \|a Hochschulschrift \|2 gnd-content
856	4	2	\|m B:DE-101 \|q application/pdf \|u http://d-nb.info/1169447325/04 \|3 Inhaltsverzeichnis
856	4	2	\|m DNB Datenaustausch \|q application/pdf \|u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030932055&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA \|3 Inhaltsverzeichnis
943	1		\|a oai:aleph.bib-bvb.de:BVB01-030932055

Datensatz im Suchindex

DE-BY-UBR_call_number	23/19.0496
DE-BY-UBR_katkey	6119557
DE-BY-UBR_location	UB Magazin
DE-BY-UBR_media_number	069041084712
_version_	1835107019461230592
adam_text	INDEX OF CONTENT ACKNOWLEDGMENT........................................................................................................IV ABBREVIATIONS..................... VI ZUSAMMENFASSUNG....................................................................................................VIII SUMMARY .... . ........................................................................................................................X 1 1 N TRO D U C TIO N ......................................................................................................................1 1.1 EXTENDING HEALTHY LIFESPAN BY DIETARY RESTRICTION (DR)....................................2 1.1.1 SIGNALING PATHWAYS AND TRANSCRIPTIONAL NETWORKS INVOLVED IN THE ORGANISMAL RESPONSE TO DR.......................................................................................................... 3 1.1.2 CONSERVED EFFECTS OF DR IN MOUSE MODELS OF REDUCED SOMATOTROPIC SIGNALING AND MTOR ACTIVITY..................................................................................................... 5 1.2 THE AGEING EPIGENOME............................................................................... 7 1.2.1 DNA METHYLATION.............................................................................................. 8 1.3 AIMS OF THE THESIS................................................................................................17 2 M E TH O D S.............................................................................. 18 2.1 ANIMAL HUSBANDRY AND DATASET GENERATION ................................................ 19 2.1.1 ANIMAL HUSBANDRY AND DR PROTOCOL................................................................19 2.1.2 RNA-SEQUENCING (RNA-SEQ) MEASUREMENT.....................................................20 2.1.3 BS-SEQ MEASUREMENT......................................................................................20 2.1.4 TRIGLYCERIDE LIPIDOME MEASUREMENT..............................................................21 2.2 PUBLISHED ANNOTATION AND SEQUENCING DATASETS ........................ 22 2.2.1 PUBLISHED WGBS-SEQ DATA...............................................................................22 2.2.2 PUBLISHED RNA-SEQ DATA................................................................................. 22 2.2.3 PUBLISHED COCHIP-SEQ DATA............................................................................. 23 2.2.4 HISTONE MODIFICATION CHIP-SEQ PEAKS............................................................. 23 2.2.5 CPG ISLAND ANNOTATION.................................................................................... 23 2.3 DATA ANALYSIS AND STATISTICAL METHODS................................ . .... . ..... . ................. 24 2.3.1 RNA-SEQ ANALYSIS............................................................................................24 2.3.2 WGBS-SEQ QUANTIFICATION AND DIFFERENTIAL METHYLATION ANALYSIS .................... 25 2.3.3 FILTERING RAW DATASETS AND DEFINITION OF DMRS ............................................... 27 2.3.4 COMPARING AGE-RELATED METHYLATION CHANGES UNDER AL AND DR ..................... 27 2.3.5 DEFINITION OF GENOMIC AND EPIGENETIC ELEMENTS.............................................28 2.3.6 COCHIP-SEQ ANALYSIS AND DEFINITION OF BIVALENT CGIS......................................29 2.3.7 DETECTING WHOLE GENE BODY METHYLATION DIFFERENCES .................................... 29 2.3.8 COMPARING DMRS ACROSS LONGEVITY INTERVENTIONS ......................................... 30 2.3.9 ENRICHMENT ANALYSES OF DMRS OVER GENOMIC AND EPIGENETIC ELEMENTS ........ 30 2.3.10 FUNCTIONAL ENRICHMENT ANALYSES OF DIFFERENTIALLY METHYLATED GENES...........31 2.3.11 MARKER REGION OF LONGEVITY ANALYSIS............................................................. 31 2.3.12 CORRELATION ANALYSIS OF METHYLATION AND TRANSCRIPTION................................31 2.3.13 COMPARATIVE TRANSCRIPTOME ANALYSIS FOR DR LIVER TISSUE AND FGFR3 KNOCKDOWN IN RT112 CELLS......................................................................................32 2.3.14 ANALYSIS OF LIPIDOMICS DATA...........................................................................33 3 DNA M E TH Y LA TIO N D Y N A M IC S U N D E R DR A N D D U RIN G AG E IN G ............................. 3 4 3.1 INTRODUCTION........................................................................................................35 3.2 RESULTS................................................................................................................. 36 3.2.1 ANIMAL HUSBANDRY, TISSUE COLLECTION AND TRANSCRIPTIONAL PROFILING................36 3.2.2 PROFILING AGE-RELATED DNA METHYLATION DYNAMICS UNDER DR..........................39 3.2.3 PROFILING THE DIET-SPECIFIC METHYLATION PATTERNS AT YOUNG AND OLD AGE .......... 50 3.2.4 DISSECTING AGE- AND DIET-RELATED SHIFTS IN HEPATIC TRIGLYCERIDE LEVELS ............ 56 3.3 DISCUSSION........................................................................................................... 60 3.3.1 DE-NOVO DNA DE/METHYLATION ACTIVITY MEDIATES THE AGE-RELATED METHYLATION DRIFT?....................................................................................................................... 61 3.3.2 ARE AGE-RELATED CHANGES IN DNA METHYLATION UNCOUPLED FROM CHROMATIN DYNAMICS?...............................................................................................................62 3.3.3 AGE-RELATED EXPRESSION AND METHYLATION CHANGES ARE NOT CORRELATED ............ 63 3.3.4 DOES DR PROTECT REGULATORS OF RAS SIGNALING FROM AGE-RELATED METHYLATION CHANGES?................................................................................................................. 64 3.3.5 DR CAUSES DIFFERENTIAL GENE BODY METHYLATION................................................65 3.3.6 DR REPROGRAMS THE SREBFL TRANSCRIPTIONAL NETWORK.......................................65 3.3.7 DR INCREASES HEPATIC LEVELS OF MEDIUM-CHAIN TRIGLYCERIDES............................67 4 DNA M E TH Y LA TIO N RE P RO G RA M M IN G IN M U RIN E LO N G EV ITY M O D E LS ................. 69 4.1 INTRODUCTION........................................................................................................70 4.2 RESULTS................................................................................................................. 71 4.2.1 CROSS-STRAIN COMPARISON OF DR-RELATED METHYLATION PATTERNS ....................... 71 4.2.2 COMPARING METHYLATION PROFILES OF AGED DR, RAPAMYCIN-TREATED AND AMES DWARF MICE.............................................................................................................. 74 4.2.3 ANALYZING THE ORIGIN AND TIMING OF INTERVENTION-RELATED METHYLATION CHANGES 81 4.2.4 JOINT BS-SEQ PROFILING IDENTIFIES CANDIDATE MARKER REGIONS OF LONGEVITY ....... 86 4.2.5 COMPARING INTERVENTION-RELATED METHYLATION AND EXPRESSION PATTERNS IN AMES DWARF AND DR FED MICE............................................................................................ 90 4.3 DISCUSSION......................................... 97 4.3.1.....EPIGENETIC REPROGRAMMING OF THE SREBFL NETWORK IS A CONSERVED FEATURE OF DR . ....................................................................................................................98 4.3.2 WHICH MECHANISMS COULD MEDIATE THE FORMATION OF COMMON METHYLATION PATTERNS?..................................................................................................................99 4.3.3 CAN COMPARATIVE METHYLATION PROFILING HELP DEVELOPING NEW BIOMARKERS OF LONGEVITY?.............................................................................................................. 100 4.3.4 EPIGENOTYPE AND PHENOTYPE OF LIFESPAN-EXTENDING INTERVENTIONS ARE CORRELATED.............................................................................................................. 101 4.3.5 INTEGRATIVE PROFILING OF METHYLATION AND TRANSCRIPTION MAY GUIDE TO NOVEL CANDIDATE GENES IN AGEING RESEARCH....................................................................... 103 5 C ONCLUSION A N D F U TU RE P E R S P E C TIV E S ....................................................................105 6 R E FE RE N C E S ....................................................................................................................109 7 S U P P LE M E N T..................................................................................................................140 CONTRIBUTIONS............................................................................................................144 EIDESSTATTLICHE ERKLAERUNG....................................................................... 145 CURRICULUM VITAE 146
any_adam_object	1
author	Hahn, Oliver
author_GND	(DE-588)1172226512
author_facet	Hahn, Oliver
author_role	aut
author_sort	Hahn, Oliver
author_variant	o h oh
building	Verbundindex
bvnumber	BV045548028
ctrlnum	(OCoLC)1135396699 (DE-599)DNB1169447325
discipline	Biologie Medizin
format	Thesis Book
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01339nam a2200361 c 4500</leader><controlfield tag="001">BV045548028</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t\|</controlfield><controlfield tag="008">190408s2018 gw a\|\|\| m\|\|\| 00\|\|\| eng d</controlfield><datafield tag="015" ind1=" " ind2=" "><subfield code="a">19,H01</subfield><subfield code="2">dnb</subfield></datafield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1169447325</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="c">Broschur</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1135396699</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DNB1169447325</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">XA-DE</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield><subfield code="a">DE-83</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">570</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">610</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Hahn, Oliver</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1172226512</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">DNA methylation dynamics in murine ageing and longevity</subfield><subfield code="c">vorgelegt von Oliver Hahn</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Köln</subfield><subfield code="c">2018</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XI, 144 Seiten</subfield><subfield code="b">Illustrationen</subfield><subfield code="c">21 cm</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Universität zu Köln</subfield><subfield code="d">2018</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">B:DE-101</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://d-nb.info/1169447325/04</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030932055&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="943" ind1="1" ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-030932055</subfield></datafield></record></collection>
genre	(DE-588)4113937-9 Hochschulschrift gnd-content
genre_facet	Hochschulschrift
id	DE-604.BV045548028
illustrated	Illustrated
indexdate	2024-12-20T18:30:01Z
institution	BVB
language	English
oai_aleph_id	oai:aleph.bib-bvb.de:BVB01-030932055
oclc_num	1135396699
open_access_boolean
owner	DE-355 DE-BY-UBR DE-83
owner_facet	DE-355 DE-BY-UBR DE-83
physical	XI, 144 Seiten Illustrationen 21 cm
publishDate	2018
publishDateSearch	2018
publishDateSort	2018
record_format	marc
spellingShingle	Hahn, Oliver DNA methylation dynamics in murine ageing and longevity
subject_GND	(DE-588)4113937-9
title	DNA methylation dynamics in murine ageing and longevity
title_auth	DNA methylation dynamics in murine ageing and longevity
title_exact_search	DNA methylation dynamics in murine ageing and longevity
title_full	DNA methylation dynamics in murine ageing and longevity vorgelegt von Oliver Hahn
title_fullStr	DNA methylation dynamics in murine ageing and longevity vorgelegt von Oliver Hahn
title_full_unstemmed	DNA methylation dynamics in murine ageing and longevity vorgelegt von Oliver Hahn
title_short	DNA methylation dynamics in murine ageing and longevity
title_sort	dna methylation dynamics in murine ageing and longevity
topic_facet	Hochschulschrift
url	http://d-nb.info/1169447325/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030932055&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
work_keys_str_mv	AT hahnoliver dnamethylationdynamicsinmurineageingandlongevity

Verfügbarkeit

‌

Per Fernleihe bestellen
Inhaltsverzeichnis