The Heterochromatin Protein 1 positively regulates euchromatic gene expression by RNA binding

ABSTRACTHeterochromatin is essential in all eukaryotes to maintain genome integrity, long-term gene repression and to help chromosome segregation during mitosis. However, heterochromatin regions must be restricted by boundary elements to avoid its spreading over actively transcribed loci. In Plasmodium falciparum, facultative heterochromatin is important to regulate parasite virulence, antigenic variation and transmission. However, the underlying molecular mechanisms regulating repressive regions remain unknown. To investigate this topic, we chose the ap2-g gene, which forms a strictly delimited and independent heterochromatin island. Using electrophoretic motility shift assay (EMSA) we identified an ap2-g exon element at the 3’ end binding nuclear protein complexes. Upon replacement of this region by a gfp gene, we observed a shift in the heterochromatin boundary resulting in HP1 (Heterochromatin Protein 1) spreading over ∼2 additional kb downstream. We used this DNA element to purify candidate proteins followed by proteomic analysis. The identified complexes were found to be enriched in RNA-binding proteins, pointing to a potential role of RNA in the regulation of the ap2-g 3’ heterochromatin boundary. Our results provide insight into the unexplored topic of heterochromatin biology in P. falciparum and identify a DNA element within the master regulator of sexual commitment modulating heterochromatin spreading.

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Genetic factors controlling white gene expression of the transposon AR4-24 at a telomere in Drosophila melanogaster

Genome ◽

10.1139/g02-074 ◽

2002 ◽

Vol 45 (6) ◽

pp. 1025-1034 ◽

Cited By ~ 2

Author(s):

M L Balasov

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Y Chromosome ◽

Genetic Factors ◽

Position Effect ◽

Position Effect Variegation ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Effect Variegation ◽

Restricted Pattern

The position effect of the AR 4-24 P[white, rosy] transposon was studied at cytological position 60F. Three copies of the transposon (within ~50-kb region) resulted in a spatially restricted pattern of white variegation. This pattern was modified by temperature and by removal of the Y chromosome, suggesting that it was due to classical heterochromatin-induced position effect variegation (PEV). In contrast with classical PEV, extra dose of the heterochromatin protein 1 (HP1) suppressed white variegation and one dose enhanced it. The effect of Pc-G, trx-G, and other PEV suppressors was also tested. It was found that E(Pc)1, TrlR85, and mutations of Su(z)2C relieve AR 4-24- silencing and z1 enhances it. To explain the results obtained with these modifiers, it is proposed that PEV and telomeric position effect can counteract each other at this particular cytological site.Key words: position effect variegation, heterochromatin protein 1, Drosophila melanogaster.

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Histone H1 and heterochromatin protein 1 (HP1) regulate specific gene expression and not global transcription

Worm ◽

10.4161/worm.23703 ◽

2013 ◽

Vol 2 (2) ◽

pp. e23703 ◽

Cited By ~ 4

Author(s):

Monika Jedrusik-Bode

Keyword(s):

Gene Expression ◽

Histone H1 ◽

Specific Gene ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Specific Gene Expression

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Expression of Heterochromatin Protein 1 in the Primary Tumor of Breast Cancer Patients in the Presence or Absence of Occult Metastatic Cells in the Bone Marrow

The International Journal of Biological Markers ◽

10.1177/172460080802300404 ◽

2008 ◽

Vol 23 (4) ◽

pp. 219-224 ◽

Cited By ~ 1

Author(s):

A.P.S. Abreu ◽

C. Milani ◽

M.L.H. Katayama ◽

E.M. Barbosa ◽

L. Gomes da Fonseca ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Bone Marrow ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Heterochromatin Formation ◽

Metastatic Cells

Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family (HP1Hsα, HP1Hsβ and HP1Hsγ), which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1Hsα, HP1Hsβ and HP1Hsγ was determined by real-time RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow.

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Physical modeling of the heritability and maintenance of epigenetic modifications

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1920499117 ◽

2020 ◽

Vol 117 (34) ◽

pp. 20423-20429 ◽

Cited By ~ 1

Author(s):

Sarah H. Sandholtz ◽

Quinn MacPherson ◽

Andrew J. Spakowitz

Keyword(s):

Gene Expression ◽

Physical Modeling ◽

Histone H3 ◽

Epigenetic Modifications ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Chromosomal Organization ◽

Chromatin Compaction ◽

Physical Mechanisms ◽

Epigenetic Code

We develop a predictive theoretical model of the physical mechanisms that govern the heritability and maintenance of epigenetic modifications. This model focuses on a particular modification, methylation of lysine-9 of histone H3 (H3K9), which is one of the most representative and critical epigenetic marks that affects chromatin organization and gene expression. Our model combines the effect of segregation and compaction on chromosomal organization with the effect of the interaction between proteins that compact the chromatin (heterochromatin protein 1) and the methyltransferases that affect methyl spreading. Our chromatin model demonstrates that a block of H3K9 methylations in the epigenetic sequence determines the compaction state at any particular location in the chromatin. Using our predictive model for chromatin compaction, we develop a methylation model to address the reestablishment of the methylation sequence following DNA replication. Our model reliably maintains methylation over generations, thereby establishing the robustness of the epigenetic code.

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Heterochromatin Protein 1 (HP1a) Positively Regulates Euchromatic Gene Expression through RNA Transcript Association and Interaction with hnRNPs in Drosophila

PLoS Genetics ◽

10.1371/journal.pgen.1000670 ◽

2009 ◽

Vol 5 (10) ◽

pp. e1000670 ◽

Cited By ~ 98

Author(s):

Lucia Piacentini ◽

Laura Fanti ◽

Rodolfo Negri ◽

Valerio Del Vescovo ◽

Alessandro Fatica ◽

...

Keyword(s):

Gene Expression ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Rna Transcript

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HP1B is a euchromatic Drosophila HP1 homolog with links to metabolism

10.1101/372094 ◽

2018 ◽

Author(s):

Benjamin B. Mills ◽

Andrew D. Thomas ◽

Nicole C. Riddle

Keyword(s):

Gene Expression ◽

Genome Stability ◽

Regulation Of Gene Expression ◽

Activity Levels ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Regulation Of Metabolism ◽

Animal Activity ◽

Drosophila Homolog ◽

Hp1 Proteins

ABSTRACTHeterochromatin Protein 1 (HP1) proteins are an important family of chromosomal proteins conserved among all major eukaryotic lineages. While HP1 proteins are best known for their role in heterochromatin, many HP1 proteins function in euchromatin as well. As a group, HP1 proteins carry out diverse functions, playing roles in the regulation of gene expression, genome stability, chromatin structure, and DNA repair. While the heterochromatic HP1 proteins are well studied, our knowledge of HP1 proteins with euchromatic distribution is lagging behind. We have created the first mutations in HP1B, a Drosophila HP1 protein with euchromatic function, and the Drosophila homolog most closely related to mammalian HP1α, HP1β, and HP1γ. We find that HP1B is a non-essential protein in Drosophila, with mutations affecting fertility and animal activity levels. In addition, animals lacking HP1B show altered food intake and higher body fat levels. Gene expression analysis of animals lacking HP1B demonstrates that genes with functions in various metabolic processes are affected primarily by HP1B loss. Our findings suggest that there is a link between the chromatin protein HP1B and the regulation of metabolism.

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KAP1 is an antiparallel dimer with a natively functional asymmetry

10.1101/553511 ◽

2019 ◽

Cited By ~ 2

Author(s):

Giulia Fonti ◽

Maria J. Marcaida ◽

Louise C. Bryan ◽

Sylvain Traeger ◽

Alexandra S. Kalantzi ◽

...

Keyword(s):

Gene Expression ◽

Single Molecule ◽

Binding Sites ◽

Mammalian Cells ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Krab Domain ◽

Sumo Ligase ◽

Functional Implications ◽

Expression In Mammalian Cells

AbstractKAP1 (KRAB-domain associated protein 1) plays a fundamental role in regulating gene expression in mammalian cells by recruiting different transcription factors and altering the chromatin state. In doing so, KAP1 acts both as a platform for macromolecular interactions and as an E3 SUMO ligase. This work sheds light on the overall organization of the full-length protein combining solution scattering diffraction data, integrative modeling and single-molecule experiments. We show that KAP1 is an elongated antiparallel dimer with a native asymmetry at the C-terminal domain. This conformation supports our finding that the RING domain contributes to KAP1 auto-SUMOylation. Importantly, this intrinsic asymmetry has key functional implications for the KAP1 network of interactions, as the heterochromatin protein 1 (HP1) occupies only one of the two putative HP1 binding sites on the KAP1 dimer, resulting in an unexpected stoichiometry, even in the context of chromatin fibers.

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The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

Current Gene Therapy ◽

10.2174/1566523219666190716092203 ◽

2019 ◽

Vol 19 (4) ◽

pp. 255-263 ◽

Cited By ~ 13

Author(s):

Yuangang Wu ◽

Xiaoxi Lu ◽

Bin Shen ◽

Yi Zeng

Keyword(s):

Gene Expression ◽

Gene Therapy ◽

Extracellular Matrix ◽

Inflammatory Reaction ◽

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Protein Translation ◽

Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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