Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure

Xingwu Lu; Sandeep N. Wontakal; Alexander V. Emelyanov; Patrick Morcillo; Alexander Y. Konev; Dmitry V. Fyodorov; Arthur I. Skoultchi

doi:10.1101/gad.1749309

Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA

Abstract

We generated mutant alleles of Drosophila melanogaster in which expression of the linker histone H1 can be down-regulated over a wide range by RNAi. When the H1 protein level is reduced to ∼20% of the level in wild-type larvae, lethality occurs in the late larval – pupal stages of development. Here we show that H1 has an important function in gene regulation within or near heterochromatin. It is a strong dominant suppressor of position effect variegation (PEV). Similar to other suppressors of PEV, H1 is simultaneously involved in both the repression of euchromatic genes brought to the vicinity of pericentric heterochromatin and the activation of heterochromatic genes that depend on their pericentric localization for maximal transcriptional activity. Studies of H1-depleted salivary gland polytene chromosomes show that H1 participates in several fundamental aspects of chromosome structure and function. First, H1 is required for heterochromatin structural integrity and the deposition or maintenance of major pericentric heterochromatin-associated histone marks, including H3K9Me₂ and H4K20Me₂. Second, H1 also plays an unexpected role in the alignment of endoreplicated sister chromatids. Finally, H1 is essential for organization of pericentric regions of all polytene chromosomes into a single chromocenter. Thus, linker histone H1 is essential in Drosophila and plays a fundamental role in the architecture and activity of chromosomes in vivo.

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Footnotes

↵1 Present addresses: 1Departamento de Genética, Universidad de Valencia, Doctor Moliner 50, E46100 Burjassot, Valencia, Spain;
↵2 Molecular and Radiation Biophysics Department, St. Petersburgh Nuclear Physics Institute, Gatchina 188300, Russia.
↵3 Corresponding authors.

↵E-MAIL dfyodoro{at}aecom.yu.edu; FAX (718) 430-8574.
↵4 E-MAIL skoultch{at}ecom.yu.edu; FAX (718) 430-8574.
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1749309.
Supplemental material is available at http://www.genesdev.org.
- Received October 6, 2008.
- Accepted January 5, 2009.