Abstract

Elucidation of the biological role of linker histone (H1) and heterochromatin protein 1 (HP1) in mammals has been difficult owing to the existence of a least 11 distinct H1 and three HP1 subtypes in mice. Caenorhabditis elegans possesses two HP1 homologues (HPL-1 and HPL-2) and eight H1 variants. Remarkably, one of eight H1 variants, HIS-24, is important for C. elegans development. Therefore we decided to analyse in parallel the transcriptional profiles of HIS-24, HPL-1/-2 deficient animals, and their phenotype, since hpl-1, hpl-2, and his-24 deficient nematodes are viable. Global transcriptional analysis of the double and triple mutants revealed that HPL proteins and HIS-24 play gene-specific roles, rather than a general repressive function. We showed that HIS-24 acts synergistically with HPL to allow normal reproduction, somatic gonad development, and vulval cell fate decision. Furthermore, the hpl-2; his-24 double mutant animals displayed abnormal development of the male tail and ectopic expression of C. elegans HOM-C/Hox genes (egl-5 and mab-5), which are involved in the developmental patterning of male mating structures. We found that HPL-2 and the methylated form of HIS-24 specifically interact with the histone H3 K27 region in the trimethylated state, and HIS-24 associates with the egl-5 and mab-5 genes. Our results establish the interplay between HPL-1/-2 and HIS-24 proteins in the regulation of positional identity in C. elegans males.

Highlights

  • Linker histone H1 and heterochromatin protein heterochromatin protein 1 (HP1) are involved in numerous processes ranging from stabilizing heterochromatin condensation to the regulation of gene expression [1,2,3,4,5]

  • Recent studies have shown a physical interaction between H1 and HP1; the biological role of histone H1 and HP1 is not well understood

  • We show that the loss of both HP1 and H1 alters the expression of a small subset of genes

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Summary

Introduction

Linker histone H1 and heterochromatin protein HP1 are involved in numerous processes ranging from stabilizing heterochromatin condensation to the regulation of gene expression [1,2,3,4,5]. The functions of HP1 and H1 proteins are mainly dependent on the cell type in which particular variants are expressed. The number of H1 (11) and HP1 variants (3) presents difficulties in studying the effect of H1 and HP1 depletion in mice, some data has emerged [3,7,8,9,10]. Loss of HP1b results in defective development of neuromuscular junctions and the cerebral cortex [10], whereas depletion of three of eleven H1 genes causes lethality connected with a very broad range of defects in mice [11,12]. H1 is necessary to establish and maintain the DNA methylation pattern in a subset of genes including the reproductive homeobox (Rhox) gene cluster [13]

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