Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase.
Recent discoveries of histone demethylases demonstrate that histone methylation is reversible. However, mechanisms governing the targeting and regulation of histone demethylation remain elusive. Here we report that a Drosophila melanogaster JmjC domain-containing protein, dKDM4A, is a histone H3K36 demethylase. dKDM4A specifically demethylates H3K36me2 and H3K36me3 both in vitro and in vivo. Affinity purification and mass spectrometry analysis revealed that heterochromatin protein 1a (HP1a) associates with dKDMA4A. We found that the chromo shadow domain of HP1a and a HP1-interacting motif of dKDM4A are responsible for this interaction. HP1a stimulates the histone H3K36 demethylation activity of dKDM4A, and this stimulation depends on the H3K9me-binding motif of HP1a. Finally, we provide in vivo evidence suggesting that HP1a and dKDM4A interact with each other and that loss of HP1a leads to an increased level of histone H3K36me3. Collectively, these results suggest a function of HP1a in transcription facilitating H3K36 demethylation at transcribed and/or heterochromatin regions.
Lin
Chia-Hui
CH
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Li
Bing
B
Swanson
Selene
S
Zhang
Ying
Y
Florens
Laurence
L
Washburn
Michael P
MP
Abmayr
Susan M
SM
Workman
Jerry L
JL
D020816:Amino Acid Motifs; D000818:Animals; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D016384:Consensus Sequence; D019281:Dimerization; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology*; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism*; D007814:Larva / Q000201:enzymology; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D056466:Histone Demethylases; C534109:KDM4A protein, Drosophila; D010089:Oxidoreductases, N-Demethylating; D008239:Lysine