Details

Autor(en) / Beteiligte

• Huang, Fu
• Ramakrishnan, Saravanan
• Pokhrel, Srijana
• Pflueger, Christian
• Parnell, Timothy J.
• Kasten, Margaret M.
• Currie, Simon L.
• Bhachech, Niraja
• Horikoshi, Masami
• Graves, Barbara J.
• Cairns, Bradley R.
• Bhaskara, Srividya
• Chandrasekharan, Mahesh B.

Titel

Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination

Ist Teil von

• The Journal of biological chemistry, 2015-11, Vol.290 (48), p.28760-28777

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Histone H3 lysine 4 (H3K4) methylation is a dynamic modification. In budding yeast, H3K4 methylation is catalyzed by the Set1-COMPASS methyltransferase complex and is removed by Jhd2, a JMJC domain family demethylase. The catalytic JmjC and JmjN domains of Jhd2 have the ability to remove all three degrees (mono-, di-, and tri-) of H3K4 methylation. Jhd2 also contains a plant homeodomain (PHD) finger required for its chromatin association and H3K4 demethylase functions. The Jhd2 PHD finger associates with chromatin independent of H3K4 methylation and the H3 N-terminal tail. Therefore, how Jhd2 associates with chromatin to perform H3K4 demethylation has remained unknown. We report a novel interaction between the Jhd2 PHD finger and histone H2A. Two residues in H2A (Phe-26 and Glu-57) serve as a binding site for Jhd2 in vitro and mediate its chromatin association and H3K4 demethylase functions in vivo. Using RNA sequencing, we have identified the functional target genes for Jhd2 and the H2A Phe-26 and Glu-57 residues. We demonstrate that H2A Phe-26 and Glu-57 residues control chromatin association and H3K4 demethylase functions of Jhd2 during positive or negative regulation of transcription at target genes. Importantly, we show that H2B Lys-123 ubiquitination blocks Jhd2 from accessing its binding site on chromatin, and thereby, we have uncovered a second mechanism by which H2B ubiquitination contributes to the trans-histone regulation of H3K4 methylation. Overall, our study provides novel insights into the chromatin binding dynamics and H3K4 demethylase functions of Jhd2. Background: The Jhd2 PHD finger is required for H3K4 demethylation, but how it contributes to chromatin binding is not known. Results: Mutating two H2A residues impacts chromatin association and H3K4 demethylation by Jhd2. Conclusion: The PHD finger-H2A interaction controls Jhd2 functions. Significance: Histone H2A is a novel recognition target for the PHD finger, and it contributes to the chromatin binding dynamics, enzymatic activities, and transcriptional regulatory functions of Jhd2.