Polycomb Group Regulation of Hox Gene Expression in C. elegans

Ross, Jen; Zarkower, David

doi:10.1016/s1534-5807(03)00135-7

Cited by 57 publications

(70 citation statements)

References 59 publications

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“…Maintenance of a repressed or an activated Hox transcriptional status has long been attributed to members of the PcG and Trithorax protein families (55,56), which execute their functions through chromatin modification. In this study, we describe a repressive role for YY1 in regulating Hoxd4 expression.…”

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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“…In addition to a role in germline development (Fong et al, 2002), the MES-2/MES-6 complex is also involved in transcriptional repression of Hox genes (Ross and Zarkower, 2003). To determine whether the MES-2/MES-6 complex and the putative SOP-2/SOR-1 complex function together in repression of Hox genes, we compared the expression pattern of Hox reporter genes in sop-2(bx91); mes-2/mes-6(RNAi) mutants with those in single mutants.…”

Section: Sop-2 Synergistically Interacts With the Mes-2/mes-6 Complexmentioning

confidence: 99%

“…Furthermore, although the ESC/E(Z) complex is found (e.g. mes-2 and mes-6), mutations in these genes result in only mild homeotic defects (Korf et al, 1998;Holdeman et al, 1998;Ross and Zarkower, 2003). Nevertheless, C. elegans Hox genes are subject to global repression.…”

Section: Introductionmentioning

confidence: 99%

RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex inC. elegans

et al. 2006

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We describe the identification and characterization of a novel PcG gene in C. elegans, sor-1, which is involved in global repression of Hox genes. sor-1 encodes a novel protein with an RNA-binding activity. We provide evidence that SOR-1 and the previously identified RNA-binding protein SOP-2 may constitute an RNA-binding complex in Hox gene repression. SOR-1 and SOP-2 directly interact with each other and are colocalized in nuclear bodies. The localization of SOR-1 depends on SOP-2. Surprisingly, homologs of SOR-1 and SOP-2 are not found in other organisms, including the congeneric species C. briggsae, suggesting an unexpected lack of evolutionary constraint on an essential global gene regulatory system.

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“…The normal development of the C. elegans male tails requires SOP-2, MES-2/-3/-6 (PcG genes) and lin-49/lin-59 (trithoraxrelated genes). As it is depicted in Figure 2, the misregulation of mab-5 and egl-5 is associated with the defects of ray development in lin-49, lin-59, SOP-2, and MESmutants [61,62] . In C. elegans as well as in Drosophila, PcG proteins operate as transcription repressors, whereas trithorax proteins operate as transcription activators [63] .…”

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confidence: 99%

Analysis of the Hox epigenetic code

Ezziane¹

2012

WJCO

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Archetypes of histone modifications associated with diverse chromosomal states that regulate access to DNA are leading the hypothesis of the histone code (or epigenetic code). However, it is still not evident how these post-translational modifications of histone tails lead to changes in chromatin structure. Histone modifications are able to activate and/or inactivate several genes and can be transmitted to next generation cells due to an epigenetic memory. The challenging issue is to identify or "decrypt" the code used to transmit these modifications to descent cells. Here, an attempt is made to describe how histone modifications operate as part of histone code that stipulates patterns of gene expression. This papers emphasizes particularly on the correlation between histone modifications and patterns of Hox gene expression in Caenorhabditis elegans . This work serves as an example to illustrate the power of the epigenetic machinery and its use in drug design and discovery.

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Polycomb Group Regulation of Hox Gene Expression in C. elegans

Cited by 57 publications

References 59 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

RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex inC. elegans

Analysis of the Hox epigenetic code

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