Tissue-specific chromatin-binding patterns of Caenorhabditis elegans heterochromatin proteins HPL-1 and HPL-2 reveal differential roles in the regulation of gene expression

Abstract Heterochromatin is characterized by an enrichment of repetitive elements and low gene density and is often maintained in a repressed state across cell division and differentiation. The silencing is mainly regulated by repressive histone marks such as H3K9 and H3K27 methylated forms and the heterochromatin protein 1 (HP1) family. Here, we analyzed in a tissue-specific manner the binding profile of the two HP1 homologs in Caenorhabditis elegans, HPL-1 and HPL-2, at the L4 developmental stage. We identified the genome-wide binding profile of intestinal and hypodermal HPL-2 and intestinal HPL-1 and compared them with heterochromatin marks and other features. HPL-2 associated preferentially to the distal arms of autosomes and correlated positively with the methylated forms of H3K9 and H3K27. HPL-1 was also enriched in regions containing H3K9me3 and H3K27me3 but exhibited a more even distribution between autosome arms and centers. HPL-2 showed a differential tissue-specific enrichment for repetitive elements conversely with HPL-1, which exhibited a poor association. Finally, we found a significant intersection of genomic regions bound by the BLMP-1/PRDM1 transcription factor and intestinal HPL-1, suggesting a corepressive role during cell differentiation. Our study uncovers both shared and singular properties of conserved HP1 proteins, providing information about genomic binding preferences in relation to their role as heterochromatic markers. The heterochromatin protein 1 (HP1) family regulates the transcriptional repression of numerous genes. C. elegans has two HP1 homologs: HPL-1 and HPL-2. Here, de la Cruis Ruiz et al. analyze the genome-wide binding profiles of HPL-1 in the intestine and HPL-2 in the intestine and hypodermis at the L4 developmental stage, showing that chromosomal distribution differs between HPL-1 and HPL-2. Further comparisons of heterochromatin marks, tissue-specific transcriptomes, and other features demonstrate tissue-specific and unique roles for HPL-1 and HPL-2.