NCBI Summary:
This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
General function
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Cellular localization
Nuclear
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Ovarian function
Early embryo development
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The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition. Torres-Campana D et al. (2020) Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Ma P et al. Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks, but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely a result of increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double-mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and nonhistone proteins in oocyte development.
PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a specific expression and localisation pattern during meiosis
Madsen B,et al .
PLU-1, a large multi-domain nuclear protein with strong transcriptional repression activity, is a member of the ARID family of DNA binding proteins. In previous studies, high levels of expression of Plu-1 mRNA and PLU-1 protein were detected in breast cancers, while expression in normal adult tissues was detected only in the testis, ovary and transiently in the mammary gland of the pregnant female. Due to its high levels of expression in the testis and to its specific relationship to cancer, PLU-1 has been proposed to belong to the family of testis-cancer antigens. In this study we attempted to determine putative functions for PLU-1 during spermatogenesis. To address this, we analysed the pattern of expression and localisation of this protein in mouse testicular cells during postnatal development and adulthood. Using in situ hybridisation and immunostaining of testis sections we show that Plu-1 mRNA and PLU-1 protein are both highly expressed in the mitotic spermatogonia. Expression is reduced dramatically in the early prophase I stages (zygotene, leptotene), but reappears at pachytene and is still detectable in diplotene cells. We also found that PLU-1 localises diffusely over the nucleus, which indicates a potential chromatin binding ability of this protein. Consistent with this notion, we found that PLU-1 is present in the chromatin fraction in biochemical cell fractionation experiments using both somatic and meiotic cells. Our data point to a role for PLU-1 in meiotic transcription, which may be restricted to certain meiotic stages and may be mediated by the ability of this protein to associate with the chromatin.