Synergistic recognition of an epigenetic DNA element by Pleiohomeotic and a Polycomb core complex

Mohd‐Sarip, Adone; Cléard, Fabienne; Mishra, Rakesh K.; Karch, François; Verrijzer, C. Peter

doi:10.1101/gad.347005

Cited by 82 publications

(93 citation statements)

References 28 publications

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“…The fly homolog of YY1, Pleiohomeotic, binds Polycomb-response elements and recruits two types of PcG complexes, one of which contains the fly homolog of MEL18, posterior sex combs (PSC) (61). Recently, data from Srinivasan and Atchison (44) demonstrate that YY1 binds to Polycomb-response elements in Drosophila and subsequently recruits other PcG proteins to DNA.…”

Section: Discussionmentioning

confidence: 99%

Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation

Kobrossy

Rastegar

Featherstone

2006

Journal of Biological Chemistry

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Correct patterning of the antero-posterior axis of the embryonic trunk is dependent on spatiotemporally restricted Hox gene expression. In this study, we identified components of the Hoxd4 P1 promoter directing expression in neurally differentiating retinoic acid-treated P19 cells. We mapped three nucleosomes that are subsequently remodeled into an open chromatin state upon retinoic acid-induced Hoxd4 transcription. These nucleosomes spanned the Hoxd4 transcriptional start site in addition to a GC-rich positive regulatory element located 3 to the initiation site. We further identified two major cis-acting regulatory elements. An autoregulatory element was shown to recruit HOXD4 and its cofactor PBX1 and to positively regulate Hoxd4 expression in differentiating P19 cells. Conversely, the Polycomb group (PcG) protein Ying-Yang 1 (YY1) binds to an internucleosomal linker and represses Hoxd4 transcription before and during transcriptional activation. Sequential chromatin immunoprecipitation studies revealed that the PcG protein MEL18 was co-recruited with YY1 only in undifferentiated P19 cells, suggesting a role for MEL18 in silencing Hoxd4 transcription in undifferentiated P19 cells. This study links for the first time local chromatin remodeling events that take place during transcriptional activation with the dynamics of transcription factor association and DNA accessibility at a Hox regulatory region.Hox gene transcriptional activation marks the onset of an intricate series of events leading to proper embryonic patterning in all animals. The products of Hox genes, homeodomain-containing HOX transcription factors, are essential in specifying antero-posterior positional identity, hindbrain development, limb formation, and numerous additional morphogenetic and organogenetic events (1, 2). Given their crucial role in embryonic development, the genes encoding HOX proteins are highly conserved throughout the animal kingdom, and their expression is tightly regulated (3). In mammals, 39 Hox genes are organized into four clusters, each located on a different chromosome (1). Comparison of the clusters reveals 13 possible gene positions, although none of the clusters retains a full complement of 13 genes. Hox genes occupying the same positions are termed paralogs, sharing high sequence identity and functional redundancy. One can assign a 3Ј and a 5Ј end to a cluster since all genes are transcribed in the same direction. A unique feature of Hox gene clusters is a process termed "colinearity," correlating both the timing of transcriptional activation and the anterior expression borders with the position of a particular Hox gene along a cluster (4). Therefore, genes located more 3Ј are expressed earlier and have a more anterior expression border than genes located more 5Ј along the cluster. This observation and several other studies have led to the hypothesis that a sequential opening of chromatin, starting at the 3Ј end of a cluster and moving successively 5Ј, leads to the release of silencing, first at the 3Ј end, and seque...

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Section: Discussionmentioning

confidence: 99%

Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation

Kobrossy

Rastegar

Featherstone

2006

Journal of Biological Chemistry

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“…YY1 is a homolog of the Drosophila pleiohomeotic (PHO) protein which is a Polycomb Group (PcG) protein involved in silencing of developmental genes. (55) YY1 interacts with another PcG protein, EED and this protein interacts with histone methylase EZH2, which carries out trimethylation of histone H3-K27. (56) In undifferentiated mouse myoblasts, endogenous EZH2 is associated with YY1 and both it and YY1 were detected, along with the histone deacetylase HDAC1, at genomic regions of silent muscle-specific genes.…”

Section: Introductionmentioning

confidence: 99%

Regulation of mammalian gene expression by retroelements and non‐coding tandem repeats

Tomilin

2008

BioEssays

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Genomes of higher eukaryotes contain abundant non‐coding repeated sequences whose overall biological impact is unclear. They comprise two categories. The first consists of retrotransposon‐derived elements. These are three major families of retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene‐rich regions and are found in promoters of genes while LINEs are concentrated in gene‐poor regions and are depleted from promoters. The second class consists of non‐coding tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with mammalian centromeres, heterochromatin and telomeres. Terminal TTAGGG arrays are involved in telomere capping and satellite DNAs are located in heterochromatin, which is implicated in transcription silencing by gene repositioning (relocalization). It is unknown whether interstitial TTAGGG sequences, which are present in many vertebrates, have a function. Here, evidence will be presented that retroelements and TTAGGG arrays are involved in regulation of gene expression. Retroelements can provide binding sites for transcription factors and protect promoter CpG islands from repressive chromatin modifications, and may be also involved in nuclear compartmentalization of transcriptionally active and inactive domains. Interstitial telomere‐like sequences can form dynamically maintained three‐dimensional nuclear networks of transcriptionally inactive domains, which may be involved in transcription silencing like classic heterochromatin. BioEssays 30:338–348, 2008. © 2008 Wiley Periodicals, Inc.

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“…RGD (underlined) is the consensus for the site that is required for association of PCC. When RGD was mutated, both the cooperative binding of Pho with PCC and PSS mediated by the iab-7 PRE were abolished (Mohd-Sarip et al 2005).…”

Section: Pre1mentioning

confidence: 99%

“…In contrast, none of the Pho sites contain a perfect match to the RGD sequence required for recruitment of PCC in vitro (Mohd-Sarip et al 2005). We introduced mutations that disrupt Pho binding into the Pho3 and Pho4 sites individually and together in PRE1.…”

Section: Pre1mentioning

confidence: 99%

Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

Brown

Kassis

2013

Genetics

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Polycomb group response elements (PREs) play an essential role in gene regulation by the Polycomb group (PcG) repressor proteins in Drosophila. PREs are required for the recruitment and maintenance of repression by the PcG proteins. PREs are made up of binding sites for multiple DNA-binding proteins, but it is still unclear what combination(s) of binding sites is required for PRE activity.Here we compare the binding sites and activities of two closely linked yet separable PREs of the Drosophila engrailed (en) gene, PRE1 and PRE2. Both PRE1 and PRE2 contain binding sites for multiple PRE-DNA-binding proteins, but the number, arrangement, and spacing of the sites differs between the two PREs. These differences have functional consequences. Both PRE1 and PRE2 mediate pairing-sensitive silencing of mini-white, a functional assay for PcG repression; however, PRE1 requires two binding sites for Pleiohomeotic (Pho), whereas PRE2 requires only one Pho-binding site for this activity. Furthermore, for full pairing-sensitive silencing activity, PRE1 requires an AT-rich region not found in PRE2. These two PREs behave differently in a PRE embryonic and larval reporter construct inserted at an identical location in the genome. Our data illustrate the diversity of architecture and function of PREs.

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Synergistic recognition of an epigenetic DNA element by Pleiohomeotic and a Polycomb core complex

Cited by 82 publications

References 28 publications

Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation

Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation

Regulation of mammalian gene expression by retroelements and non‐coding tandem repeats

Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

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