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BEGIN:VEVENT
DTSTAMP:20260506T221320Z
DTSTART;VALUE=DATE-TIME:20230918T123000
DTEND;VALUE=DATE-TIME:20230918T133000
SUMMARY:BMS Seminars: The PerpleXing Germ Line: Why and How to Turn a Chr
 omosome OFF and ON Again and Transcriptional activation by pioneer trans
 cription factors in mammalian pre-implantation development
TZID:Europe/London
UID:20230918-8a1785d88a2bbd20018a2cee54d94cd0@warwick.ac.uk
CREATED:20230825T134211Z
DESCRIPTION:The PerpleXing Germ Line: Why and How to Turn a Chromosome OF
 F and ON Again\, Dr Bernhard Payer\, Centre for Genomic Regulation (CRG)
 \, Barcelona\, Spain Abstract: The mammalian germline is characterised b
 y extensive epigenetic reprogramming during development into eggs and sp
 erm. Specifically\, the epigenome requires resetting before parental mar
 ks can be established and transmitted to the next generation. In the fem
 ale germline\, X-chromosome inactivation and reactivation are among the 
 most prominent epigenetic reprogramming events\, yet little is known abo
 ut their kinetics and biological function. Here I present how we study X
 -inactivation and reactivation dynamics using an in vitro system of prim
 ordial germ cell-like cell (PGCLC) differentiation in ovarian organoids.
  We find that X-inactivation in PGCLCs is moderate compared to somatic c
 ells\, and characterised by many genes escaping X-inactivation. Subseque
 ntly we observe step-wise X-reactivation\, which is mostly completed dur
 ing meiotic prophase I. Importantly\, we find that PGCLCs\, which fail X
 -inactivation or reactivate too rapidly display impaired meiotic potenti
 al. Now we are testing\, if X-dosage control is a direct functional requ
 irement or rather a diagnostic mark for proper germ cell differentiation
 . It appears that active and inactive X-chromosome states present stage-
 specific constraints that are crucial for the normal development of fema
 le germ cells towards meiosis and oogenesis. Biography: In my lab we stu
 dy the importance of epigenetic reprogramming for pluripotency and germ 
 cell development. A major focus has been the iPSC-reprogramming system\,
  with which we identified molecular regulators and the role of 3D-genome
  structure for X-chromosome reactivation (Bauer\, Nature Comm 2021\; Gen
 eroso\, PNAS 2023\, Barrero\, BioRxiv 2023). The other main area of inte
 rest concerns female germ cell development\, where we identified PRDM14 
 as important for X-reactivation in mice (Mallol\, Epigenetics & Chromati
 n 2019). Using in vitro derived ovarian organoids from mouse ESCs\, we f
 ound that the correct X-chromosome dynamics to be a critical indicator o
 f meiotic and oogenic potential (Severino\, EMBO J 2022). In collaborati
 on with the clinic\, we generated patient-specific hiPSCs for human in v
 itro germ cell modeling and studied human oocyte aging by single-cell RN
 A-Seq (Llonch\, Aging Cell 2021) ---- Transcriptional activation by pion
 eer transcription factors in mammalian pre-implantation development\, Dr
  Wataru Kobayashi\, MPI of Biochemistry\, Bayern\, Germany Abstract: Fol
 lowing fertilization\, the totipotency is gradually decreased during cle
 avage divisions until reaching a pluripotency or differentiated state. I
 n this process\, transcription factors (TFs) play crucial roles in succe
 ssful pre-implantation development. Notably\, specialized TFs\, called p
 ioneer transcription factors (pTFs) have unique abilities to modulate ep
 igenetic and chromatin states by recruiting chromatin remodelers and his
 tone modifiers. Mammalian embryos are initially awakened during zygotic 
 genome activation (ZGA) and further develop into blastocysts including t
 hree cell lineages. However\, how pTFs/TFs control transcriptional regul
 ation to achieve proper pre-implantation development is largely unknown.
  Orphan nuclear receptor Nr5a2 is expressed in murine oocytes and embryo
 s\, but its function during pre-implantation development is unknown. Lev
 eraging the low-input genomic method\, we discovered that Nr5a2 function
 s as a pTF that opens the chromatin during ZGA in mouse embryos (Gassler
 *\, Kobayashi* et al.\, Science\, 2022). We recently found that the chro
 matin binding of Nr5a2 is dynamically changed during the totipotency-to-
 pluripotency transition (Kobayashi et al.\, unpublished). We further det
 ermined the cryo-EM structure of the human NR5A2-nucleosome complex and 
 revealed its pioneering activity at the atomic resolution (Kobayashi et 
 al.\, bioRxiv\, 2023). Taken together\, my works opened new opportunitie
 s for understanding the function of TF in mammalian embryos. Biography: 
 My broad interest is how transcription factors control transcriptional n
 etworks to determine cell potentials and fate during mammalian developme
 nt. I have gained expertise in biochemistry and structural biology throu
 gh my Ph.D. and postdoctoral research in the laboratory of Dr. Hitoshi K
 urumizaka at Waseda University. I am a postdoctoral fellow in Dr. Kikuë 
 Tachibana’s group at the Max Planck Institute of Biochemistry. I expande
 d my expertise in embryology and genomics and combined them with biochem
 ical & structural approaches to uncover the molecular mechanism of trans
 criptional regulations in mammalian pre-implantation embryos.
LOCATION:
CATEGORIES:BiomedicalSciences,DivisionalSeminars,CSRL
LAST-MODIFIED:20230825T134211Z
ORGANIZER;CN=Jas Bains:
END:VEVENT
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