Reference Report

Reference
Citation	Li, L., Greer, C., Eisenman, R.N., Secombe, J. (2010). Essential functions of the histone demethylase lid. PLoS Genet. 6(11): e1001221. (Export to RIS)
FlyBase ID	FBrf0212448
Publication Type	Research paper
PubMed ID	21124823
PubMed Abstract	Drosophila Little imaginal discs (Lid) is a recently described member of the JmjC domain class of histone demethylases that specifically targets trimethylated histone H3 lysine 4 (H3K4me3). To understand its biological function, we have utilized a series of Lid deletions and point mutations to assess the role that each domain plays in histone demethylation, in animal viability, and in cell growth mediated by the transcription factor dMyc. Strikingly, we find that lid mutants are rescued to adulthood by either wildtype or enzymatically inactive Lid expressed under the control of its endogenous promoter, demonstrating that Lid's demethylase activity is not essential for development. In contrast, ubiquitous expression of UAS-Lid transgenes lacking its JmjN, C-terminal PHD domain, and C(5)HC(2) zinc finger were unable to rescue lid homozygous mutants, indicating that these domains carry out Lid's essential developmental functions. Although Lid-dependent demethylase activity is not essential, dynamic removal of H3K4me3 may still be an important component of development, as we have observed a genetic interaction between lid and another H3K4me3 demethylase, dKDM2. We also show that Lid's essential C-terminal PHD finger binds specifically to di- and trimethylated H3K4 and that this activity is required for Lid to function in dMyc-induced cell growth. Taken together, our findings highlight the importance of Lid function in the regulated removal and recognition of H3K4me3 during development.
DOI	10.1371/journal.pgen.1001221
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Alleles (18)
	dm^Scer\UAS.cZa Kdm2^DG12810 lid¹⁰⁴²⁴ lid^{C1296A.Scer\UAS.P\T} lid^gJmjC.mut lid^gWT lid^{JmjC.mut.Scer\UAS.P\T} lid^k06801 lid^{Scer\UAS.P\T.cSa} lid^unspecified lid^{ΔARID.Scer\UAS.P\T} lid^{ΔC5HC2.Scer\UAS.P\T} lid^{ΔJmjN.Scer\UAS.P\T} lid^{ΔPHD1.Scer\UAS.P\T} lid^{ΔPHD2.Scer\UAS.P\T} lid^{ΔPHD3.Scer\UAS.P\T} Scer\GAL4^Act.PU Scer\GAL4^GMR.PF
Constructs (14)
	P{Act-GAL4.U} P{GAL4-ninaE.GMR} P{gLid-JmjC.mut} P{gLid-WT} P{UAS-dm.Z} P{UASp-lid.C1296A} P{UASp-lid.JmjC.mut} P{UASp-lid.S} P{UASp-lid.ΔARID} P{UASp-lid.ΔC5HC2} P{UASp-lid.ΔJmjN} P{UASp-lid.ΔPHD1} P{UASp-lid.ΔPHD2} P{UASp-lid.ΔPHD3}
Genes (5)
	dm His3 Kdm2 lid Scer\GAL4
Natural transposons (1)
	P-element