KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity

Bridoux, Laure; Bergiers, Isabelle; Draime, Amandine; Halbout, Mathias; Deneyer, Noémie; Twizere, Jean-Claude; Rezsöhazy, René

doi:10.1016/j.bbagrm.2015.08.006

Cited by 14 publications

(15 citation statements)

References 54 publications

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“…In the cytoplasm, HOXB9 could act as translation regulator, as it has been demonstrated for HOXA9 [79]. Changes in HOXB9 distribution between the nucleus and cytoplasm could also reflect a way to regulate its transcriptional activity, as it has previously been reported for HOXA2 [80]. …”

Section: Discussionmentioning

confidence: 69%

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

et al. 2016

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BackgroundWe previously showed that the homeodomain transcription factor HOXB9 is expressed in mammalian oocytes and early embryos. However, a systematic and exhaustive study of the localization of the HOXB9 protein, and HOX proteins in general, during mammalian early embryonic development has so far never been performed.ResultsThe distribution of HOXB9 proteins in oocytes and the early embryo was characterized by immunofluorescence from the immature oocyte stage to the peri-gastrulation period in both the mouse and the bovine. HOXB9 was detected at all studied stages with a dynamic expression pattern. Its distribution was well conserved between the two species until the blastocyst stage and was mainly nuclear. From that stage on, trophoblastic cells always showed a strong nuclear staining, while the inner cell mass and the derived cell lines showed important dynamic variations both in staining intensity and in intra-cellular localization. Indeed, HOXB9 appeared to be progressively downregulated in epiblast cells and only reappeared after gastrulation had well progressed. The protein was also detected in the primitive endoderm and its derivatives with a distinctive presence in apical vacuoles of mouse visceral endoderm cells.ConclusionsTogether, these results could suggest the existence of unsuspected functions for HOXB9 during early embryonic development in mammals.

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Section: Discussionmentioning

confidence: 69%

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

et al. 2016

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“…Gateway® entry vectors for mouse Hoxb1 and Hoxb2 (Bridoux & al. 2015 PubMed PMID: 26303204), human HOXA3 and HOXC4 (http://horfdb.dfci.harvard.edu/hv7/) were used to generate mammalian expression vectors for FLAG-HOX (v1899 destination vector) using the gateway technology (Barrios-Rodiles et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

“…HEK293 cells were transfected as above, using 500ng each of FLAG/GST constructs per well. Proteins were collected 48 hours after transfection and co-precipitation performed as described in (Bridoux et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

Bridoux

Zarrineh

Mallen

et al. 2019

Preprint

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19Gene expression programs determine cell fate in embryonic development and their 20 dysregulation results in disease. Transcription factors (TFs) control gene expression by 21 binding to enhancers, but how TFs select and activate their target enhancers is still unclear. 22HOX TFs share conserved homeodomains with highly similar sequence recognition 23properties, yet they impart the identity of different animal body parts. To understand how 24 HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and 25 HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with 26 TALE TFs and selectively target different subsets of a broad TALE chromatin platform. 27Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high 28 confidence, tissue-specific binding events, which bear the mark of active enhancers. We 29 propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate 30 tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected 31 enhancers. 32 33 Introduction 34 Gene expression programs instruct and maintain cell fate in embryonic development and 35 adult tissue homeostasis. Transcription factors (TFs) control gene expression by binding to 36 enhancers (Reiter et al., 2017; Spitz and Furlong, 2012). However, we still have no clear 37 idea of how TFs select their precise sets of target enhancers. While TFs contain DNA 38 binding domains which recognize DNA in a sequence-specific manner, these interactions 39 are typically insufficient to direct a TF to its functional targets. 40Transcriptional regulation is mediated by TFs working together, rather than in isolation. The 41 widespread occurrence of collaborative TF binding is imposed by chromatin. A single TF 42 cannot easily compete with nucleosomes to access DNA, but multiple TFs that recognize 43 closely spaced binding sites can effectively displace nucleosomes and indirectly facilitate 44 each other's binding (Mirny, 2010; Moyle-Heyrman et al., 2011). Such indirect cooperativity 45 can also result in TFs recognizing low affinity sites, i.e. sites that deviate from their optimal 46 3 consensus in vitro (Farley et al., 2015). Recent observations indicate that TF cooperativity 47 does not end at binding enhancers: clusters of enhancer-bound TFs concentrate co-48 activators and other nuclear factors via dynamic fuzzy interactions, driven by their 49 intrinsically disordered regions (IDRs). IDRs function in molecular recognition and mediate 50 the interaction with a diversity of regulatory proteins (Cumberworth et al., 2013; Staby et al., 51 2017) to promote the liquid-liquid phase transition associated with gene activation (Boija et 52 al., 2018). Thus, the formation, on DNA segments, of regulatory complexes made of different 53 combinations of factors, is key to activation of gene expression. These distinct combinations 54 of TFs produce virtually inexhaustible flavours of gene expression and cell fate (Spitz and 55 Furlong, 2012).56...

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“…The plasmids pML‐ EphA2 ‐r4‐Luc , pML‐ Hoxb1‐ARE ‐Luc , pCMV‐ Lacz , the pEXP‐FLAG(Nter)‐ Hoxa2 , pCMV‐ Pbx1 , pCS2‐ Prep1 , pEXP‐FLAG(Nter)‐ Hoxa1 , pEXP‐GST(Nter)‐ Hoxa1 , pEXP‐VC155(Nter)‐ Hoxa1 , pEXP‐FLAG(Nter)‐ Hoxa1 ΔNter , pEXP‐FLAG(Nter)‐ Hoxa1 Δ11His , pEXP‐FLAG(Nter)‐ Hoxa1 Δ71–199 and pEXP‐FLAG(Nter)‐ Hoxa1 ΔHD have all been described elsewhere. All Hoxa1 expression constructs and mutant derivatives were obtained starting from the mouse cDNA sequence coding for HOXA1 (uniprot number: http://www.uniprot.org/uniprot/P09022).…”

Section: Methodsmentioning

confidence: 99%

The O‐GlcNAc transferase OGT interacts with and post‐translationally modifies the transcription factor HOXA1

et al. 2018

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HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development. Little is known about the molecular pathways controlling HOXA1. Recent data from our group revealed distinct partner proteins interacting with HOXA1. Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription. Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1. Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.

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KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity

Cited by 14 publications

References 54 publications

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

The O‐GlcNAc transferase OGT interacts with and post‐translationally modifies the transcription factor HOXA1

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