Developmental roles of the histone lysine demethylases

Nottke, Amanda C.; Colaiácovo, Mónica P.; Shi, Yang

doi:10.1242/dev.020966

Cited by 202 publications

(174 citation statements)

References 93 publications

(188 reference statements)

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“…We isolated a zebrafish mutant whose gata1 expression is reduced and identified the responsible gene as the zebrafish homolog of Lys-specific demethylase 1 (LSD1/ KDM1A). LSD1 belongs to the FAD-dependent amine oxidases that demethylate mono-and dimethylated Lys4 (K4) and/or Lys9 (K9) within histone H3 through an oxidative process (19) and has been suggested to play key roles in multiple aspects of cell differentiation through epigenetic regulation (20).…”

mentioning

confidence: 99%

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Takeuchi

Fuse

Watanabe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The hemangioblast is a progenitor cell with the capacity to give rise to both hematopoietic and endothelial progenitors. Currently, the regulatory mechanisms underlying hemangioblast formation are being elucidated, whereas those controllers for the selection of hematopoietic or endothelial fates still remain a mystery. To answer these questions, we screened for zebrafish mutants that have defects in the hemangioblast expression of Gata1, which is never expressed in endothelial progenitors. One of the isolated mutants, it627, showed not only down-regulation of hematopoietic genes but also up-regulation of endothelial genes. We identified the gene responsible for the it627 mutant as the zebrafish homolog of Lys-specific demethylase 1 (LSD1/KDM1A). Surprisingly, the hematopoietic defects in lsd1it627 embryos were rescued by the gene knockdown of the Ets variant 2 gene (etv2), an essential regulator for vasculogenesis. Our results suggest that the LSD1-dependent shutdown of Etv2 gene expression may be a significant event required for hemangioblasts to initiate hematopoietic differentiation.

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mentioning

confidence: 99%

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Takeuchi

Fuse

Watanabe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Epigenetic marks are DNA or histone posttranslational modifications that are inherited through cell division and that inform about the transcriptional state of loci. Among histone modifications, histone lysine methylation is of particular interest in development for the broad range of processes in which it is involved, including maintenance of stem cell pluripotency, germ-line determination, cell differentiation, control of HOX genes expression, and so forth (2,3). Histone lysine methylation was considered a stable posttranslational modification until the discovery of histone demethylases.…”

mentioning

confidence: 99%

“…BRAF35 contains a high-mobility group (HMG) domain and a coiled-coil domain, but its function within the complex is not well-understood (7,10). Several functions of the LSD1-CoREST complex in differentiation and development have been reported (2). One of the best-characterized functions of the complex is its role in repression of neuronal genes in nonneuronal tissues and neuronal progenitors through its interaction with repressor factor REST (RE1 silencing transcription factor) (11,12).…”

mentioning

confidence: 99%

Control of neuronal differentiation by sumoylation of BRAF35, a subunit of the LSD1-CoREST histone demethylase complex

Ceballos-Chávez

Rivero

García-Gutiérrez³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The LSD1-CoREST histone demethylase complex is required to repress neuronal genes in nonneuronal tissues. Here we show that sumoylation of Braf35, one of the subunits of the complex, is required to maintain full repression of neuron-specific genes and for occupancy of the LSD1-CoREST complex at its gene targets. Interestingly, expression of Braf35 was sufficient to prevent neuronal differentiation induced by bHLH neurogenic transcription factors in P19 cells and in neuronal progenitors of the chicken embryo neural tube. Sumoylation of Braf35 is required for this antineurogenic activity. We also show that iBraf, a paralogue of Braf35, forms heterodimers with Braf35. Braf35-iBraf heterodimerization impairs Braf35 interaction with the LSD1-CoREST complex and inhibits Braf35 sumoylation. Consistent with these results, iBraf prevents the antineurogenic activity of Braf35 in vivo. Our data uncover a mechanism of regulation of the LSD1-CoREST complex and provide a molecular explanation for the antagonism between Braf35 and iBraf in neuronal differentiation.C ell differentiation involves large modifications of gene expression that require extensive changes of chromatin epigenetic marks (1). Epigenetic marks are DNA or histone posttranslational modifications that are inherited through cell division and that inform about the transcriptional state of loci. Among histone modifications, histone lysine methylation is of particular interest in development for the broad range of processes in which it is involved, including maintenance of stem cell pluripotency, germ-line determination, cell differentiation, control of HOX genes expression, and so forth (2, 3). Histone lysine methylation was considered a stable posttranslational modification until the discovery of histone demethylases. LSD1/KDM1 (lysine-specific demethylase 1) was the first demethylase identified and catalyzes demethylation of both di-and monomethylated lysine 4 (K4) or lysine 9 (K9) of histone H3 (H3K4me2/1 or H3K9me2/1) (4, 5). The lysine specificity of LSD1 seems to depend on its molecular partners. Thus, when LSD1 is associated with CoREST in the LSD1-CoREST corepressor complex (also called BHC, BRAF-histone deacetylase complex), the preferred substrate is H3K4me2/1, consistent with the fact that methylation of H3K4 is a mark of transcriptionaly active genes. In addition to LSD1 and CoREST, the LSD1-CoREST complex also contains HDAC1-2, BHC80, and BRAF35 (also called HMG20B) (6-9). BRAF35 contains a high-mobility group (HMG) domain and a coiled-coil domain, but its function within the complex is not well-understood (7, 10). Several functions of the LSD1-CoREST complex in differentiation and development have been reported (2). One of the best-characterized functions of the complex is its role in repression of neuronal genes in nonneuronal tissues and neuronal progenitors through its interaction with repressor factor REST (RE1 silencing transcription factor) (11,12). iBRAF (inhibitor of BRAF35, also called HMG20A) is a close paralogue of BRAF35 (13). As BRAF35...

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“…Coordination to establish the correct ''epigenetic code,'' removing or adding repressive or activating marks, plays a key role during development, and failures in either step cause dysregulation of gene expression, which has been strongly linked to different diseases (Swigut and Wysocka, 2007;Nottke et al, 2009;Herz and Shilatifard, 2010;Ho and Crabtree, 2010;Lindeman et al, 2011). However, there are few publications that associate changes in histone methylation and NC development.…”

Section: Methylationmentioning

confidence: 99%

Epigenetic landscape and miRNA involvement during neural crest development

Strobl-Mazzulla¹,

Marini²,

Buzzi³

2012

Developmental Dynamics

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The neural crest (NC) is a multipotent, migratory cell population that arises from the dorsal neural fold of vertebrate embryos. NC cells migrate extensively and differentiate into a variety of tissues, including melanocytes, bone, and cartilage of the craniofacial skeleton, peripheral and enteric neurons, glia, and smooth muscle and endocrine cells. For several years, the gene regulatory network that orchestrates NC cells development has been extensively studied. However, we have recently begun to understand that epigenetic and posttranscriptional regulation, such as miRNAs, plays important roles in NC development. In this review, we focused on some of the most recent findings on chromatin-dependent mechanisms and miRNAs regulation during vertebrate NC cells development.

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Developmental roles of the histone lysine demethylases

Cited by 202 publications

References 93 publications

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Control of neuronal differentiation by sumoylation of BRAF35, a subunit of the LSD1-CoREST histone demethylase complex

Epigenetic landscape and miRNA involvement during neural crest development

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