The Drosophila Mi-2 Chromatin-Remodeling Factor Regulates Higher-Order Chromatin Structure and Cohesin Dynamics In Vivo

• Published in: PLoS genetics Vol. 8; no. 8; p. e1002878
• Main Authors: Fasulo, Barbara, Deuring, Renate, Murawska, Magdalena, Gause, Maria, Dorighi, Kristel M., Schaaf, Cheri A., Dorsett, Dale, Brehm, Alexander, Tamkun, John W.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2012; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Animal genetics; Animals; Autoantigens - genetics; Autoantigens - metabolism; Biology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatids; Chromatin; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Cohesins; Deoxyribonucleic acid; DNA; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Fluorescence Recovery After Photobleaching; Gene expression; Genetic aspects; Insects; Interphase - genetics; Molecular genetics; Nucleosomes - genetics; Physiological aspects; Polytene Chromosomes - genetics; Protein Binding; Proteins; Salivary Glands - cytology; Salivary Glands - metabolism; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002878

dMi-2 is a highly conserved ATP-dependent chromatin-remodeling factor that regulates transcription and cell fates by altering the structure or positioning of nucleosomes. Here we report an unanticipated role for dMi-2 in the regulation of higher-order chromatin structure in Drosophila. Loss of dMi-2 function causes salivary gland polytene chromosomes to lose their characteristic banding pattern and appear more condensed than normal. Conversely, increased expression of dMi-2 triggers decondensation of polytene chromosomes accompanied by a significant increase in nuclear volume; this effect is relatively rapid and is dependent on the ATPase activity of dMi-2. Live analysis revealed that dMi-2 disrupts interactions between the aligned chromatids of salivary gland polytene chromosomes. dMi-2 and the cohesin complex are enriched at sites of active transcription; fluorescence-recovery after photobleaching (FRAP) assays showed that dMi-2 decreases stable association of cohesin with polytene chromosomes. These findings demonstrate that dMi-2 is an important regulator of both chromosome condensation and cohesin binding in interphase cells.