Whole cell proteimics of leptotene+zygotene(LZ) and pachytene+diplotene+diakinesis (PDD) of first meiosis prophase of spermatogenesis in male mouse.
Ontology highlight
ABSTRACT: 2-hydroxyglutarate (2HG) is recognized as an epigenetic regulator in cancer and some transient biological processes. Of all organs, the testis harbors the highest baseline physiological levels of 2HG, yet it’s putative functions in germ cell biology are unknown. Here we show that 2HG is generated in specific stages of spermatogenesis by the testis specific lactate dehydrogenase C (LDHC), beginning at the last stages of prophase I. Unexpectedly LDHC enters nuclei and concentrates in centromeres. LDHC-generated L-2HG controls centromere condensation and pericentromeric heterochromatin organization through multiple effects including clustering of chromocenters, centromere and chromocenter condensation and expression of satellite RNAs. These effects are rapid and specific to L but not D-2HG. In vivo depletion of L-2HG causes centromere malfunction and activation of the spindle assembly checkpoint. Our findings reveal that 2HG can directly affect centromere and pericentromeric heterochromatin conformation and function and is necessary for licensing chromosome segregation.
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Testis, Male Germ Cell
SUBMITTER:
Eli Pikarsky
LAB HEAD: Eli Pikarsky
PROVIDER: PXD039015 | Pride | 2025-05-23
REPOSITORIES: Pride
ACCESS DATA