Characterization of Drosophila melanogaster JmjC+N histone demethylases.
In this article, we characterize histone demethylase activity of the entire family of JmjC+N proteins of Drosophila melanogaster. Our results show that Lid (little imaginal discs), which is structurally homologous to JARID1, demethylates H3K4me3. However, contrary to what would be inferred from its demethylase activity, lid contributes to the establishment of transcriptionally competent chromatin states as: (i) is required for histone H3 acetylation; (ii) contributes to expression of the homoeotic gene Ultrabithorax (Ubx); and (iii) antagonizes heterochromatin-mediated gene silencing (PEV). These results, which are consistent with the identification of lid as a trithorax group (trxG) gene, are discussed in the context of current models for the contribution of H3K4me3 to the regulation of gene expression. Here, we also show that the two Drosophila JMJD2 homologues, dJMJD2(1)/CG15835 and dJMJD2(2)/CG33182, are capable of demethylating both H3K9me3 and H3K36me3. dJMJD2(1)/CG15835 regulates heterochromatin organization, as its over-expression induces spreading of HP1, out of heterochromatin, into euchromatin, without affecting the actual pattern of histone modifications of heterochromatin. dJMJD2(1)/CG15835 is excluded from heterochromatin and localizes to multiple euchromatic sites, where it regulates H3K36 methylation. These results indicate that dJMJD2(1)/CG15835 contributes to delimit hetero- and euchromatic territories through the regulation of H3K36 methylation in euchromatin. On the other hand, dJARID2/CG3654 shows no demethylase activity on H3K4me3, H3K9me3, H3K27me3, H3K36me3 and H4K20me3.
Lloret-Llinares
Marta
M
Institute of Molecular Biology of Barcelona, CSIC, Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Josep Samitier, 1-5, 08028 Barcelona, Spain.
Carré
Clément
C
Vaquero
Alejandro
A
de Olano
Natalia
N
Azorín
Fernando
F
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D029721:Drosophila Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D022041:Euchromatin / Q000737:chemistry; D020868:Gene Silencing; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D022041:Euchromatin; D006657:Histones; C452193:heterochromatin protein 1, Drosophila; D056466:Histone Demethylases; C518655:Lid protein, Drosophila; C534109:KDM4A protein, Drosophila; D010089:Oxidoreductases, N-Demethylating; D011495:Histone-Lysine N-Methyltransferase