Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity.

Colmenares, Serafin U; Swenson, Joel M; Langley, Sasha A; Kennedy, Cameron; Costes, Sylvain V; Karpen, Gary H

Colmenares, Serafin U; Swenson, Joel M; Langley, Sasha A; Kennedy, Cameron; Costes, Sylvain V; Karpen, Gary H.

Afiliación

Colmenares SU; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: sucolmenares@lbl.gov.
Swenson JM; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA.
Langley SA; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Kennedy C; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Costes SV; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Karpen GH; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA.

Dev Cell ; 42(2): 156-169.e5, 2017 07 24.

Article en En | MEDLINE | ID: mdl-28743002

RESUMEN

Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair. We demonstrate that dKDM4A demethylase activity is dispensable for PEV. In contrast, dKDM4A enzymatic activity is required to relocate heterochromatic double-strand breaks outside the domain, as well as for organismal survival when DNA repair is compromised. Finally, DNA damage triggers dKDM4A-dependent changes in the levels of H3K56me3, suggesting that dKDM4A demethylates this heterochromatic mark to facilitate repair. We conclude that dKDM4A, in addition to its previously characterized role in euchromatin, utilizes both enzymatic and structural mechanisms to regulate heterochromatin organization and functions.

Asunto(s)

Proteínas de Drosophila/metabolismo; Drosophila melanogaster/citología; Drosophila melanogaster/enzimología; Heterocromatina/metabolismo; Histona Demetilasas/metabolismo; Animales; Biocatálisis; Ciclo Celular/genética; Puntos de Control del Ciclo Celular/genética; Efectos de la Posición Cromosómica/genética; Roturas del ADN de Doble Cadena; Reparación del ADN/genética; Proteínas de Drosophila/química; Drosophila melanogaster/genética; Fertilidad/genética; Regulación de la Expresión Génica; Silenciador del Gen; Histonas/metabolismo; Lisina/metabolismo; Metilación; Mutación/genética; Dominios Proteicos; Transcripción Genética

Palabras clave

DNA repair; Drosophila; H3K36me3; H3K56me3; HP1a; dKDM4A; heterochromatin; histone demethylase; position-effect variegation; Î³H2Av

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heterocromatina / Proteínas de Drosophila / Drosophila melanogaster / Histona Demetilasas Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google