Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish

Hadrys, Thorsten; Punnamoottil, Beena; Pieper, Mareike; Kikuta, Hiroshi; Pézeron, Guillaume; Becker, Thomas; Prince, Victoria; Baker, R.; Rinkwitz, Silke

doi:10.1016/j.ydbio.2006.04.446

Cited by 25 publications

(24 citation statements)

References 80 publications

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“…To this end, the spatiotemporal activity of hoxb4a was documented from 1–30 days in specific subgroups of r7–8 neurons using high-resolution confocal microscopy in an enhancer-trap zebrafish line with yellow fluorescent protein (YFP) retroviral insertion [27], [28] that closely reproduces the endogenous mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

Mosaic hoxb4a Neuronal Pleiotropism in Zebrafish Caudal Hindbrain

Punnamoottil

Rinkwitz

et al. 2009

PLoS ONE

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To better understand how individual genes and experience influence behavior, the role of a single homeotic unit, hoxb4a, was comprehensively analyzed in vivo by clonal and retrograde fluorescent labeling of caudal hindbrain neurons in a zebrafish enhancer-trap YFP line. A quantitative spatiotemporal neuronal atlas showed hoxb4a activity to be highly variable and mosaic in rhombomere 7–8 reticular, motoneuronal and precerebellar nuclei with expression decreasing differentially in all subgroups through juvenile stages. The extensive Hox mosaicism and widespread pleiotropism demonstrate that the same transcriptional protein plays a role in the development of circuits that drive behaviors from autonomic through motor function including cerebellar regulation. We propose that the continuous presence of hoxb4a positive neurons may provide a developmental plasticity for behavior-specific circuits to accommodate experience- and growth-related changes. Hence, the ubiquitous hoxb4a pleitropism and modularity likely offer an adaptable transcriptional element for circuit modification during both growth and evolution.

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Section: Introductionmentioning

confidence: 99%

Mosaic hoxb4a Neuronal Pleiotropism in Zebrafish Caudal Hindbrain

Punnamoottil

Rinkwitz

et al. 2009

PLoS ONE

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“…Sharing of cis-regulatory elements has been previously described for genes in the HoxB and C clusters, however, it remains unclear whether mir-196b shares regulatory elements with the neighboring Hox genes or if its expression is controlled by Mll independently of Hoxa9 and Hoxa10. 38,39 Embryoid bodies contain a highly heterogenous population of cells. To more specifically investigate hematopoietic cells we isolated CD41 ϩ cells from day 10 embryoid bodies.…”

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confidence: 99%

Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization

Popovic

Riesbeck

Velu

et al. 2009

Blood

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Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene produce chimeric proteins that cause abnormal expression of a subset of HOX genes and leukemia development. Here, we show that MLL normally regulates expression of mir-196b, a hematopoietic microRNA located within the HoxA cluster , in a pattern similar to that of the surrounding 5 Hox genes, Hoxa9 and Hoxa10, during embryonic stem (ES) cell differentiation. Within the hematopoietic lineage, mir-196b is most abundant in short-term hematopoietic stem cells and is down-regulated in more differentiated hematopoietic cells. Leukemogenic MLL fusion proteins cause overexpression of mir-196b, while treatment of MLL-AF9 transformed bone marrow cells with mir-196-specific antagomir abrogates their replating potential in methylcellulose. This demonstrates that mir-196b function is necessary for MLL fusion-mediated im-mortalization. Furthermore, overexpres-sion of mir-196b was found specifically in patients with MLL associated leukemias as determined from analysis of 55 primary leukemia samples. Overexpression of mir-196b in bone marrow progenitor cells leads to increased proliferative capacity and survival, as well as a partial block in differentiation. Our results suggest a mechanism whereby increased expression of mir-196b by MLL fusion proteins significantly contributes to leukemia development. (Blood. 2009;113:3314-3322) Introduction The Mixed Lineage Leukemia (MLL) gene is commonly involved in chromosome translocations that cause leukemia. 1,2 MLL-associated leukemias can be myeloid, lymphoid or biphenotypic, depending on the partner gene to which MLL is fused. 3 There have been more than 60 different MLL fusion partners isolated to date and, in most cases, overexpression of a subset of HOX genes is a hallmark of the disease. 4 HOX genes are transcription factors that play an important role during development and hematopoiesis. 5,6 Humans have 13 paralogous groups of HOX genes clustered on 4 different chromosomes. Expression of HOX genes is spatially and temporally regulated with 3 genes expressed earlier and having a more anterior boundary of expression. 5 Similarly, expression of HOX genes is tightly regulated during hemato-poiesis. Genes located at the 3 end of the cluster are down-regulated as CD34 cells become lineage-specific progenitors while 5 genes, like HOXA10, are turned off only after cells progress to the more differentiated CD34 stage. 7 MLL regulates expression of some of the HOX genes at the chromatin level by binding to the promoters and recruiting various transcriptional regulators. 8-10 However, what happens at the molecular level in the presence of the leukemogenic fusion proteins to cause HOX overexpression is still poorly understood. Among 6800 genes analyzed by expression microarrays, overex-pression of HOXA9 was the most correlative marker of poor prognosis in acute myeloid leukemia patients. 11 Immortalization of bone marrow progenitors by the MLL fusion protein MLL-ENL is dependent on the presence of Hoxa9 and Hoxa7ge...

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“…[32][33][34][35] HI-C sequencing data, 36 a comprehensive technique to capture the conformation of genomes, 32 shows that CEBPA is located in a 170-kb conserved TAD (labeled 2 in Figure 1A and supplemental Figure 1A) on chromosome 19. This TAD also contains CEBPG and the promoter of SLC7A10, located 59 and 39 of CEBPA, respectively ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%