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UID:1268@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20250305T130000

DTEND;TZID=Asia/Jerusalem:20250305T140000

DTSTAMP:20250220T130905Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-dor-sh
 alev/

SUMMARY:PhD Graduate Seminar-Dor Shalev [No Categories]
DESCRIPTION:Location: Biology auditorium and by ZOOM:https://technion.zoom.
 us/j/94977953065  \n Affiliation: \n Host:Prof. PHILIPPA MELAMED\,Prof. YA
 EL MANDEL-GUTFREUND  \n The roles and regulation of Mkrn3 in mouse hypotha
 lamic neurons\n\nMakorin Ring Finger Protein 3 (MKRN3) functions as a "pub
 ertal brake\," and loss-of-function mutations in MKRN3 are the most common
  genetic cause of central precocious puberty\, which sees activation of th
 e reproductive axis at an abnormally young age. MKRN3 expression in the br
 ain decreases significantly leading up to puberty\, suggesting a repressiv
 e role on the hypothalamic GnRH which comprises the master regulator of re
 production. However\, the factors driving this drop in MKRN3 levels\, as w
 ell as its downstream targets are not known. Through extensive computation
 al analysis of bulk and single cell RNA sequencing data from rodent brain 
 samples across development\, combined with experimental studies in a mouse
  GnRH neuronal cell line\, we identified the developmentally upregulated r
 eceptor\, Acvr1c\, as a repressor of Mkrn3 expression though activation of
  Smad2/3 signaling. This repression involves the recruitment of the transc
 ription factor Kap1\, and the induction of repressive histone modification
 s at the Mkrn3 gene locus. Additionally\, we generated and integrated vari
 ous multi-omics data from GnRH-producing neurons: Mkrn3 protein and RNA in
 teractomes\, as well as proteome and transcriptome data following Mkrn3 ov
 erexpression. These analyses revealed a predominant role for Mkrn3 in regu
 lating a large number of proteins\, primarily via translation. Moreover\, 
 we found that Mkrn3 binds Gnrh1 mRNA\, along with Igf2bp2 which interacts 
 directly with Mkrn3\, providing novel insights into the mechanisms through
  which Mkrn3 affects pubertal timing. 
LOCATION:Biology auditorium and by ZOOM:https://technion.zoom.us/j/94977953
 065

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