Novel Roles of <i>Caenorhabditis elegans</i> Heterochromatin Protein HP1 and Linker Histone in the Regulation of Innate Immune Gene Expression

Studencka, Maja; Konzer, Anne; Moneron, Gael; Wenzel, Dirk; Opitz, Lennart; Salinas-Riester, Gabriela; Bedet, Cécile; Krüger, Marcus; Hell, Stefan W.; Wiśniewski, Jacek R.; Schmidt, Henning; Palladino, Francesca; Schulze, Ekkehard; Jedrusik-Bode, Monika

doi:10.1128/mcb.05229-11

Cited by 37 publications

(64 citation statements)

References 63 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its Ume6-dependent recruitment to early meiotic genes supports a growing body of evidence that linker histones, although ubiquitous throughout the genome, may play specific roles in the repression of related genes via transcription factor recruitment (10,33,37,48,52). In addition, Hho1 plays a role in genome compaction specifically in the late stages of sporulation.…”

Section: Discussionmentioning

confidence: 71%

“…Alternatively, Hho1 may be phosphorylated to affect the interaction, as linker histone association to chromatin is dynamic and affected by phosphorylation in higher eukaryotes (34). Moreover, the heterochromatin protein HP1 has been shown to recruit specifically methylated H1 to the promoters of genes involved in the immune response in Caenorhabditis elegans (48). Thus, it is possible that in S. cerevisiae, posttranslational modification of Hho1 or Ume6 may alter their association.…”

Section: Discussionmentioning

confidence: 99%

“…The linker histone represses transcription in vitro, but its transcriptional role in vivo has been the subject of debate (7,24). Although H1 has historically been associated with chromatin compaction and general repression, several recent studies have implicated the linker histone in the repression of specific genes via recruitment by transcription factors (10,33,37,45,48,52).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae

Bryant

Govin

Zhang

et al. 2012

Molecular and Cellular Biology

View full text Add to dashboard Cite

fThe differentiation of gametes involves dramatic changes to chromatin, affecting transcription, meiosis, and cell morphology. Sporulation in Saccharomyces cerevisiae shares many chromatin features with spermatogenesis, including a 10-fold compaction of the nucleus. To identify new proteins involved in spore nuclear organization, we purified chromatin from mature spores and discovered a significant enrichment of the linker histone (Hho1). The function of Hho1 has proven to be elusive during vegetative growth, but here we demonstrate its requirement for efficient sporulation and full compaction of the spore genome. Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNA. We also link Hho1 function to the transcription factor Ume6, the master repressor of early meiotic genes. Hho1 and Ume6 are depleted during meiosis, and analysis of published ChIP-chip data obtained during vegetative growth reveals a high binding correlation of both proteins at promoters of early meiotic genes. Moreover, Ume6 promotes binding of Hho1 to meiotic gene promoters. Thus, Hho1 may play a dual role during sporulation: Hho1 and Ume6 depletion facilitates the onset of meiosis via activation of Ume6-repressed early meiotic genes, whereas Hho1 enrichment in mature spores contributes to spore genome compaction. Gametogenesis is a complex, highly regulated differentiation program that is integral to the survival of higher eukaryotes. Mammalian spermatogenesis begins with DNA replication and recombination, ultimately generating four genetically unique haploid cells. The postmeiotic differentiation of spermatozoa involves a complete reorganization of the chromatin and a dramatic compaction of the nucleus that prepare the genome for passage to a new generation (16,30). In fact, specific combinations of histone posttranslational modifications (PTMs) are found at genes encoding important developmental regulators (5,20).Gametogenesis in Saccharomyces cerevisiae, or sporulation, shares several chromatin features with mammalian spermatogenesis, namely, drastic compaction of the nucleus and stage-specific appearance of histone PTMs such as phosphorylation of histone H3 at serine 10 (H3S10ph), H3T11ph, and H4S1ph (17, 31). Sporulation takes place in diploid yeast deprived of nitrogen and a fermentable carbon source (15,39). Under these starvation conditions, yeast cells enter a meiotic program similar to that found in mammalian spermatogenesis. During the postmeiotic phase, cell and nuclear volumes are substantially decreased, the genome is compacted, transcription is silenced, and a protective spore wall is synthesized. The resultant quiescent spore is able to survive unfavorable growth conditions of heat, dehydration, and chemical insult. When a fermentable carbon source is reintroduced, spores are induced to reenter the cell cycle through a process called germination, characterized by a spec...

show abstract

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae

Bryant

Govin

Zhang

et al. 2012

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Therefore, the absence of HPL-2 improves survival following the induction of acute ER stress by two distinct stressors. Importantly, increased resistance to ER stress does not reflect a general resistance to stress conditions, as hpl-2 mutants are inheritently sensitive to thermal stress (8), more sensitive to osmotic stress (10), but unaltered in their response to oxidative stress (7).…”

Section: Resultsmentioning

confidence: 99%

The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER homeostasis through the UPR and hormesis

Kozlowski

Garvis

Bedet

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Cellular adaptation to environmental changes and stress relies on a wide range of regulatory mechanisms that are tightly controlled at several levels, including transcription. Chromatin structure and chromatin binding proteins are important factors contributing to the transcriptional response to stress. However, it remains largely unknown to what extent specific chromatin factors influence the response to distinct forms of stress in a developmental context. One of the best characterized stress response pathways is the unfolded protein response (UPR), which is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). Here, we show that Caenorhabditis elegans heterochromatin protein like-2 (HPL-2), the homolog of heterochromatin protein 1 (HP1), downregulates the UPR in the intestine. Inactivation of HPL-2 results in an enhanced resistance to ER stress dependent on the X-box binding protein 1 (XBP-1)/inositol requiring enzyme 1 branch of the UPR and the closely related process of autophagy. Increased resistance to ER stress in animals lacking HPL-2 is associated with increased basal levels of XBP-1 activation and ER chaperone expression under physiological conditions, which may in turn activate an adaptive response known as ER hormesis. HPL-2 expression in intestinal cells is sufficient to rescue stress resistance, whereas expression in neuronal cells negatively influenced the ER stress response through a cell-nonautonomous mechanism. We further show that the retinoblastoma protein homolog LIN-35 and the LIN-13 zinc finger protein act in the same pathway as HPL-2 to limit the ER stress response. Altogether, our results point to multiple functions for HP1 in different cell types to maintain ER homeostasis.

show abstract

“…Our previous work showed that recruitment of the hPaf1 complex to HAdV genes required hBre1 (6). The hPaf1 complex comprises 6 subunits: Cdc73, Ctr9, Leo1, hPaf1, Rtf1, and Ski8 (17)(18)(19)(20). Previous work has shown that hBre1 binds to the hPaf1 complex (16).…”

Section: Resultsmentioning

confidence: 99%

Adenovirus E1A Recruits the Human Paf1 Complex To Enhance Transcriptional Elongation

Fonseca

Cohen

Mymryk

2014

J Virol

View full text Add to dashboard Cite

During infection by human adenovirus (HAdV), the proteins encoded by the early region 1A (E1A) gene bind and appropriate components of the cellular transcriptional machinery to activate the transcription of viral early genes. Previously, we identified roles for the human Bre1 (hBre1) and hPaf1 complexes in E1A-mediated transcriptional activation of HAdV early genes. Here we show that E1A binds hBre1 directly and that this complex targets the hPaf1 complex via the Rtf1 subunit. Depletion of hPaf1 reduces E1A-dependent activation of transcription from the E2e, E3, and E4 viral transcription units, and this does not result from a reduced ability of RNA polymerase II to be recruited to the promoter-proximal regions of these genes. In contrast, depletion of hPaf1 reduces the occupancy of RNA polymerase II across these transcription units. This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes. Together, these results indicate that E1A uses hBre1 to recruit the hPaf1 complex in order to optimally activate viral early transcription by enhancing transcriptional elongation. IMPORTANCEThis work provides the mechanism by which the hPaf1 complex contributes to E1A-dependent activation of early gene transcription. The work also demonstrates that E1A induces gene expression by stimulating transcriptional elongation, in addition to its better-characterized effects on transcriptional initiation.

show abstract

Novel Roles of Caenorhabditis elegans Heterochromatin Protein HP1 and Linker Histone in the Regulation of Innate Immune Gene Expression

Cited by 37 publications

References 63 publications

The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae

The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae

The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER homeostasis through the UPR and hormesis

Adenovirus E1A Recruits the Human Paf1 Complex To Enhance Transcriptional Elongation

Contact Info

Product

Resources

About