How HP1 Post-Translational Modifications Regulate Heterochromatin Formation and Maintenance

Gil, Raquel Sales; Vagnarelli, Paola

doi:10.3390/cells9061460

Cited by 18 publications

(15 citation statements)

References 102 publications

(133 reference statements)

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“…With mutation analyses, we identified that the HP1β-pS89 is catalyzed by CK2 in cells, which is in line with in vitro phosphorylation assay following mass spectrometry analyses ( 60 , 61 ). This phosphorylation generates a specific binding site for KAP1 that provides a link to pluripotency as KAP1 has been identified as an essential factor that represses differentiation-inducible and derepresses pluripotency-associated genes ( 57 , 62–65 ).…”

Section: Discussionsupporting

confidence: 71%

Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency

Qin

Ugur

Mulholland

et al. 2021

Nucleic Acids Research

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Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β−/− embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, HP1β is phosphorylated at serine 89 by CK2, which creates a binding site for the pluripotency regulator KAP1. This phosphorylation dependent sequestration of KAP1 in heterochromatin compartments causes a downregulation of pluripotency factors and triggers pluripotency exit. Accordingly, HP1β−/− and phospho-mutant cells exhibited impaired differentiation, while ubiquitination-deficient KAP1−/− cells had the opposite phenotype with enhanced differentiation. These results suggest that KAP1 regulates pluripotency via its ubiquitination activity. We propose that the formation of subnuclear membraneless heterochromatin compartments may serve as a dynamic reservoir to trap or release cellular factors. The sequestration of essential regulators defines a novel and active role of heterochromatin in gene regulation and represents a dynamic mode of remote control to regulate cellular processes like cell fate decisions.

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Section: Discussionsupporting

confidence: 71%

Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency

Qin

Ugur

Mulholland

et al. 2021

Nucleic Acids Research

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“…It was suggested that TFs act in a combinatorial fashion and may exhibit pleiotropic functionality [ 33 , 39 , 40 ]. Alternatively, they might interact with additional regulatory proteins [ 36 , 41 ], or undergo post-transcriptional modification like other epigenetic regulators [ 42 , 43 , 44 ].…”

Section: Dna-based Featuresmentioning

confidence: 99%

Peculiarities of Plasmodium falciparum Gene Regulation and Chromatin Structure

Watzlowik

Das

Meissner

et al. 2021

IJMS

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The highly complex life cycle of the human malaria parasite, Plasmodium falciparum, is based on an orchestrated and tightly regulated gene expression program. In general, eukaryotic transcription regulation is determined by a combination of sequence-specific transcription factors binding to regulatory DNA elements and the packaging of DNA into chromatin as an additional layer. The accessibility of regulatory DNA elements is controlled by the nucleosome occupancy and changes of their positions by an active process called nucleosome remodeling. These epigenetic mechanisms are poorly explored in P. falciparum. The parasite genome is characterized by an extraordinarily high AT-content and the distinct architecture of functional elements, and chromatin-related proteins also exhibit high sequence divergence compared to other eukaryotes. Together with the distinct biochemical properties of nucleosomes, these features suggest substantial differences in chromatin-dependent regulation. Here, we highlight the peculiarities of epigenetic mechanisms in P. falciparum, addressing chromatin structure and dynamics with respect to their impact on transcriptional control. We focus on the specialized chromatin remodeling enzymes and discuss their essential function in P. falciparum gene regulation.

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“…Also mammalian HP1 isoforms undergo specific modifications including phosphorylation, acetylation, methylation, formylation, ubiquitination, SUMOylation and citrullination (Minc et al 1999;Lomberk et al 2006;LeRoy et al 2009;Maison et al 2011;Wiese et al 2019;Sales-Gil and Vagnarelli 2020). Similarly to Drosophila HP1, each of these modifications can change HP1 functions, thus creating an epigenetic subcode that would permit different interactions of HP1 in different chromatin contexts.…”

Section: Introductionmentioning

confidence: 99%

Unravelling HP1 functions: post-transcriptional regulation of stem cell fate

2021

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Heterochromatin protein 1 (HP1) is a non-histone chromosomal protein first identified in Drosophila as a major component of constitutive heterochromatin, required for stable epigenetic gene silencing in many species including humans. Over the years, several studies have highlighted additional roles of HP1 in different cellular processes including telomere maintenance, DNA replication and repair, chromosome segregation and, surprisingly, positive regulation of gene expression. In this review, we briefly summarize past research and recent results supporting the unexpected and emerging role of HP1 in activating gene expression. In particular, we discuss the role of HP1 in post-transcriptional regulation of mRNA processing because it has proved decisive in the control of germline stem cells homeostasis in Drosophila and has certainly added a new dimension to our understanding on HP1 targeting and functions in epigenetic regulation of stem cell behaviour.

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How HP1 Post-Translational Modifications Regulate Heterochromatin Formation and Maintenance

Cited by 18 publications

References 102 publications

Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency

Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency

Peculiarities of Plasmodium falciparum Gene Regulation and Chromatin Structure

Unravelling HP1 functions: post-transcriptional regulation of stem cell fate

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