Reference Report

Reference
Citation	Chauhan, C., Zraly, C.B., Parilla, M., Diaz, M.O., Dingwall, A.K. (2012). Histone Recognition and Nuclear Receptor Co-Activator Functions of Drosophila Cara Mitad, a Homolog of the N-Terminal Portion of Mammalian MLL2 and MLL3. Development 139(11): 1997--2008. (Export to RIS)
FlyBase ID	FBrf0218263
Publication Type	Research paper
PubMed ID	22569554
PubMed Abstract	MLL2 and MLL3 histone lysine methyltransferases are conserved components of COMPASS-like co-activator complexes. In vertebrates, the paralogous MLL2 and MLL3 contain multiple domains required for epigenetic reading and writing of the histone code involved in hormone-stimulated gene programming, including receptor-binding motifs, SET methyltransferase, HMG and PHD domains. The genes encoding MLL2 and MLL3 arose from a common ancestor. Phylogenetic analyses reveal that the ancestral gene underwent a fission event in some Brachycera dipterans, including Drosophila species, creating two independent genes corresponding to the N- and C-terminal portions. In Drosophila, the C-terminal SET domain is encoded by trithorax-related (trr), which is required for hormone-dependent gene activation. We identified the cara mitad (cmi) gene, which encodes the previously undiscovered N-terminal region consisting of PHD and HMG domains and receptor-binding motifs. The cmi gene is essential and its functions are dosage sensitive. CMI associates with TRR, as well as the EcR-USP receptor, and is required for hormone-dependent transcription. Unexpectedly, although the CMI and MLL2 PHDf3 domains could bind histone H3, neither showed preference for trimethylated lysine 4. Genetic tests reveal that cmi is required for proper global trimethylation of H3K4 and that hormone-stimulated transcription requires chromatin binding by CMI, methylation of H3K4 by TRR and demethylation of H3K27 by the demethylase UTX. The evolutionary split of MLL2 into two distinct genes in Drosophila provides important insight into distinct epigenetic functions of conserved readers and writers of the histone code.
DOI	10.1242/dev.076687
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Secondary IDs	FBrf0218204
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Aberrations (3)
	Df(2R)Lpt¹ Df(2R)Lpt² Df(2R)or-BR11
Alleles (17)
	ash2^GD1374 B¹ Dcr-2^Scer\UAS.cDa Ecol\lacZ^Adh.EcRE EcR^A483T Lpt¹ Lpt^{dsRNA.Scer\UAS} Lpt^{Scer\UAS.T:Ivir\HA1} Scer\GAL4^69B Scer\GAL4^C-765 Scer\GAL4^ey.PU Scer\GAL4^unspecified trr⁴ trr^GD4501 usp^NIG.4380R Utx^NIG.5640R wds^GD9379
Constructs (11)
	P{EcRE.lacZ} P{ey-GAL4.U} P{GAL4} P{GD1374} P{GD4501} P{GD9379} P{NIG.4380R} P{NIG.5640R} P{UAS-Dcr-2.D} P{UAS-Lpt.HA} P{UAS-Lpt.IR}
Genes (18)
	ash2 B CG5339 cyp33 Dcr-2 Ecol\lacZ EcR Eip74EF Eip75B His3 Hsp27 Lpt Scer\GAL4 T:Ivir\HA1 trr usp Utx wds
Insertions (3)
	P{EPgy2}EY06424 P{GawB}69B P{GawB}C-765
Natural transposons (1)
	P-element