{"id":5984,"date":"2026-10-19T09:48:18","date_gmt":"2026-10-19T09:48:18","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-kristjan-holm-gretarsson\/"},"modified":"2026-10-19T09:48:18","modified_gmt":"2026-10-19T09:48:18","slug":"doktorsvorn-i-lif-og-laeknavisindum-kristjan-holm-gretarsson","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-kristjan-holm-gretarsson\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Kristj\u00e1n H\u00f3lm Gr\u00e9tarsson"},"content":{"rendered":"
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\u00deri\u00f0judaginn 15. desember ver Kristj\u00e1n H\u00f3lm Gr\u00e9tarsson doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Afhj\u00fapun stj\u00f3rnunarferla DNA-met\u00fdleringar \u00ed endurforritun umframerf\u00f0a snemma \u00ed f\u00f3stur\u00feroskun. <\/strong>Unraveling the mechanism of DNA methylation regulation during early embryo epigenetic reprogramming.<\/strong><\/p>\n

V\u00f6rninni ver\u00f0ur streymt:\u00a0<\/p>\n

ht<\/a>tps:\/\/livestream.com\/hi\/doktorsvornkristjanholm<\/a><\/p>\n

Andm\u00e6lendur eru dr. Miguel Branco, pr\u00f3fessor vi\u00f0 Blizzard Institute, Queen Mary University, og Hans T\u00f3mas Bj\u00f6rnsson, pr\u00f3fessor vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n

Umsj\u00f3narkennari og me\u00f0lei\u00f0beinandi var dr. Erna Magn\u00fasd\u00f3ttir d\u00f3sent og lei\u00f0beinandi var dr. Jamie Hackett, h\u00f3pstj\u00f3ri vi\u00f0 EMBL \u00ed R\u00f3m. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd dr. Alexander Aulehla, og dr. Mathieu Boulard, h\u00f3pstj\u00f3rar vi\u00f0 EMBL.<\/p>\n

Engilbert Sigur\u00f0sson, pr\u00f3fessor og deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

Fj\u00f6ldatakm\u00f6rkun: Einungis 10 manns geta veri\u00f0 \u00ed salnum \u00e1 me\u00f0an \u00e1 doktorsv\u00f6rninni stendur.<\/strong><\/p>\n

\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n

Umframerf\u00f0astj\u00f3rnpr\u00f3tein taka \u00fe\u00e1tt \u00ed a\u00f0 stj\u00f3rna mismunandi genatj\u00e1ningu og koma \u00feannig upp s\u00e9rh\u00e6f\u00f0u umframerf\u00f0amengi \u00ed frumum sem allar hafa sama erf\u00f0amengi\u00f0. \u00dea\u00f0 er mikilv\u00e6gt a\u00f0 skilja hvernig umframerf\u00f0amerkjum er stj\u00f3rna\u00f0 snemma \u00ed f\u00f3stur\u00feroskun spend\u00fdra. \u00c1 fyrstu skrefum f\u00f3stur\u00feroskunar spend\u00fdra undirgengst f\u00f3stri\u00f0 alhli\u00f0a endurr\u00f6\u00f0un umframerf\u00f0a sem fjarl\u00e6gir \u00e1unnin umframerf\u00f0amerki og jafnar \u00fat umframerf\u00f0amengin \u00ed b\u00e1\u00f0um kynfrumum foreldranna. Sl\u00edk endurr\u00f6\u00f0un umframerf\u00f0a felur \u00ed s\u00e9r v\u00ed\u00f0amiklar breytinar \u00e1 hist\u00f3num\u00f6rkum \u00e1samt \u00fev\u00ed a\u00f0 fjarl\u00e6gja og endursetja DNA-met\u00fdleringu sem tryggir \u00feroskunarh\u00e6fni f\u00f3stursins. Skilningur \u00e1 \u00feeim ferlum sem stj\u00f3rna endurr\u00f6\u00f0un e\u00f0a umframerf\u00f0ast\u00f6\u00f0u er mikilv\u00e6gur og hefur \u00fe\u00fd\u00f0ingu fyrir umframerf\u00f0ir, fj\u00f6lh\u00e6fni og umframerf\u00f0astj\u00f3rnun. Til a\u00f0 varpa lj\u00f3si \u00e1 \u00fe\u00e1 ferla sem stj\u00f3rna heildarf\u00e6rslum \u00e1 DNA-met\u00fdleringu, var eins-frumu DNA-met\u00fdleringar n\u00e6mu kl\u00f6gugeni byggt \u00e1 hlutfallslegri tj\u00e1ningu komi\u00f0 upp. \u00deetta kl\u00f6gugen var s\u00ed\u00f0an nota\u00f0 \u00ed heilmengis CRISPR skimun \u00ed stofnfrumum \u00far f\u00f3sturv\u00edsum m\u00fasa (mESC). Lykilgen og stj\u00f3rnferlar sem orsaka heildartap \u00e1 DNA-met\u00fdleringu \u00ed frumum voru fundnir og sta\u00f0festir. Me\u00f0 \u00feessu fundust yfir 20 gen sem \u00feegar \u00feau voru slegin \u00fat hvert fyrir sig, ollu r\u00f6skun \u00ed a\u00f0 fjarl\u00e6gja heildar DNA-met\u00fdleringu \u00ed frumum \u00e1samt \u00fev\u00ed a\u00f0 n\u00e1nari greining var ger\u00f0 \u00e1 hlutverkum Cop1 og Dusp6 \u00ed \u00feessu ferli.<\/p>\n

Auk \u00feess voru DPPA2 og DPPA4 skilgreind sem nau\u00f0synleg prot\u00edn til a\u00f0 vi\u00f0halda sta\u00f0bundnu umframerf\u00f0a\u00e1standi \u00ed umframerf\u00f0atilf\u00e6rslum \u00ed fj\u00f6lh\u00e6fum frumum. Me\u00f0 \u00fev\u00ed a\u00f0 fjarl\u00e6gja Dppa2 e\u00f0a Dppa4 var\u00f0 tap \u00e1 H3K4me3 og aukning \u00e1 DNA-met\u00fdleringu \u00e1 genum me\u00f0 hlutverk \u00ed f\u00f3stur\u00feroska og \u00fer\u00f3unarfr\u00e6\u00f0ilega ungum LINE1 r\u00f6\u00f0um sem DPPA2 binst vi\u00f0. \u00deessu fylgdi a\u00f0 gen me\u00f0 hlutverk \u00ed f\u00f3stur\u00feroska \u00e1unnu s\u00e9r b\u00e6landi umframerf\u00f0aminni sem olli \u00fev\u00ed a\u00f0 \u00feessi gen voru ekki virkju\u00f0 \u00ed s\u00ed\u00f0ari vefjas\u00e9rh\u00e6fingu. \u00deessi aukning \u00e1 DNA-met\u00fdleringu sem var greind g\u00e6ti veri\u00f0 mikilv\u00e6g fyrir st\u00f6\u00f0uga umframerf\u00f0a\u00fe\u00f6ggun \u00e1 DPPA2 bundnum genum me\u00f0 hlutverk \u00ed f\u00f3stur\u00feroskun og LINE1 r\u00f6\u00f0um, \u00fev\u00ed a\u00f0 fjarl\u00e6ging \u00e1 DNA-met\u00fdleringu var n\u00f3g til a\u00f0 endurvirkja genatj\u00e1ningu og H3K4me3 a\u00f0 huta til \u00feegar DPPA2 var ekki til sta\u00f0ar. DPPA2\/4 m\u00f3ta \u00fev\u00ed umframerf\u00f0amengi\u00f0 \u00ed fj\u00f6lh\u00e6fum frumum me\u00f0 \u00fev\u00ed a\u00f0 koma upp H3K4me3 og virka gegn aukningu \u00e1 DNA methyleringu, \u00feetta ferli hefur s\u00ed\u00f0an veri\u00f0 a\u00f0laga\u00f0 a\u00f0 \u00fer\u00f3unarfr\u00e6\u00f0ilega ungum LINE1 to a\u00f0 for\u00f0ast umframerf\u00f0a\u00fe\u00f6ggun \u00ed fj\u00f6lh\u00e6fum frumum. Me\u00f0 \u00feessari ritger\u00f0 er skilningur okkar aukinn \u00e1 \u00fev\u00ed hvernig umframerf\u00f0amerkjum er b\u00e6\u00f0i stj\u00f3rna\u00f0 v\u00ed\u00f0femt yfir erf\u00f0amengi\u00f0 og \u00e1 sta\u00f0bundin h\u00e1tt \u00ed erf\u00f0amenginu snemma \u00ed f\u00f3stur\u00feroskun til a\u00f0 tryggja \u00feroskunarh\u00e6fni.<\/p>\n

English abstract<\/strong><\/p>\n

Epigenetic regulators contribute to the control of distinct gene expression patterns by establishing specialized epigenomes in cells that share the same genome. How epigenetic marks are initially shaped in the early development is of great importance and incompletely understood.\u00a0During mammalian development, the embryo undergoes genome-wide epigenome remodelling which equalises the distinct parental epigenomes and resets genomic potential. This epigenetic reprogramming requires extensive chromatin modification changes, including DNA methylation erasure and reacquisition, which enables developmental competence.\u00a0Understanding the mechanisms that mediate either reprogramming or persistence of epigenetic states is currently an outstanding question and has implications for our understanding of inheritance, pluripotency, and epigenetic regulation.\u00a0To uncover the mechanisms that regulate DNA methylation dynamics, I established a single-cell ratiometric global DNA methylation reporter and coupled it with genome-wide CRISPR screening in murine embryonic stem cells (ESCs) undergoing DNA demethylation transition. Key genes and regulatory pathways that drive global DNA hypomethylation were identified and validated, revealing over 20 gene perturbations that result in impaired global demethylation. I further characterised the roles for\u00a0Cop1\u00a0and\u00a0Dusp6 in this process in detail.<\/p>\n

Additionally,\u00a0I identified Dppa2\u00a0and\u00a0Dppa4 as essential safeguards of focal epigenetic states during the epigenome transitions associated with pluripotency. Specifically, I found that deletion of\u00a0Dppa2\u00a0or\u00a0Dppa4\u00a0resulted in loss of H3K4me3 and gain of ectopic de novo DNA methylation at developmental genes and evolutionarily young LINE1 elements, which are specifically bound by DPPA2. As a result, developmental genes acquire a repressive epigenetic memory that leads to a failure to induce their appropriate activation in future lineage specification. Furthermore, the gain of DNA methylation might be important for stable epigenetic silencing at DPPA2 bound developmental genes and LINE1 elements as removal of DNA methylation causes their partial reactivation and gain of H3K4me3 in the absence of\u00a0Dppa2.\u00a0DPPA2\/4 thereby sculpt the pluripotent epigenome by facilitating H3K4me3 and bivalency to counteract de novo methylation, a function co-opted by evolutionarily young LINE1 to evade epigenetic silencing during pluripotency. This thesis represents an advance in our understanding of both how epigenomic states are globally modulated, and how they are established at specific loci, during early development to ensure genome competence multi-lineage differentiation.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Kristj\u00e1n H\u00f3lm Gr\u00e9tarsson er f\u00e6ddur \u00ed Reykjav\u00edk \u00feann 29. mars 1991. Hann h\u00f3f n\u00e1m vi\u00f0 H\u00e1sk\u00f3la \u00cdslands \u00ed l\u00edfefna- og sameindal\u00edffr\u00e6\u00f0i og \u00fatskrifa\u00f0ist me\u00f0 BS-gr\u00e1\u00f0u fr\u00e1 Raunv\u00edsindadeild \u00e1ri\u00f0 2014. Eftir \u00fea\u00f0 byrja\u00f0i hann \u00ed framhaldsn\u00e1mi \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands og lauk \u00fea\u00f0an n\u00e1mi me\u00f0 mastersgr\u00e1\u00f0u. \u00c1ri\u00f0 2016 flutti hann til \u00cdtal\u00edu og h\u00f3f vinnu vi\u00f0 doktorsverkefni sitt sem unni\u00f0 var vi\u00f0 European Molecular Biology Laboratory (EMBL) \u00ed R\u00f3m. Foreldrar Kristj\u00e1ns eru Gr\u00e9tar Bjarni Gu\u00f0j\u00f3nsson og Svava A\u00f0albj\u00f6rg Kristj\u00e1nsd\u00f3ttir.\u00a0<\/p>\n<\/div><\/div>","protected":false},"featured_media":1175,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2020-12-15T13:00:00+00:00","_phd_date_end":"2020-12-15T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Afhj\u00fapun stj\u00f3rnunarferla DNA-met\u00fdleringar \u00ed endurforritun umframerf\u00f0a snemma \u00ed f\u00f3stur\u00feroskun. 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