Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Berg, Debbie L. C. van den; Azzarelli, Roberta; Oishi, Koji; Martynoga, Ben; Urbán, Noelia; Dekkers, Dick H. W.; Demmers, Jeroen; Guillemot, François

doi:10.1016/j.neuron.2016.11.047

Cited by 66 publications

(56 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some found that Scc2 peaks overlap with those of cohesin only at enhancers and promoters (Fournier et al, 2016;Kagey et al, 2010). Others found little or no overlap with cohesin and instead detected Scc2 bound to active promoters that do not coincide with cohesin peaks (Busslinger et al, 2017;van den Berg et al, 2016;Zuin et al, 2014). Despite these differences none of the studies reported any significant co-localisation with CTCF sites where the vast majority of cohesin peaks are found.…”

Section: Introductionmentioning

confidence: 92%

“…It is not known why slightly reduced Scc2 abundance results in such severe developmental defects, but the level of cohesin on chromatin is unchanged and cohesion is unaffected in heterozygous Scc2 mice (Chien et al, 2011;Remeseiro et al, 2013). A cohesin-independent function in transcription has been suggested for Scc2 (van den Berg et al, 2016;Zuin et al, 2014) but further CdLS mutations are found in cohesin genes indicating an aetiology related to the complex (Boyle et al, 2016;Deardorff et al, 2012;Revenkova et al, 2009). These findings suggest that CdLS is not caused by a reduction in binding of cohesin to DNA but rather a change in its behaviour once loaded.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Scc2/Nipbl hops between chromosomal cohesin rings after loading

Rhodes

Mazza

Nasmyth

et al. 2017

Preprint

View full text Add to dashboard Cite

The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intrachromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin's ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin's ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and singlemolecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a "stop-and-go" or "hopping" motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

show abstract

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Scc2/Nipbl hops between chromosomal cohesin rings after loading

Rhodes

Mazza

Nasmyth

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…Early work showed that mutation of IntS4 or IntS7 resulted in lethality in Drosophila (Rutkowski and Warren 2009;Ezzeddine et al 2011), and a mutation in IntS6 was subsequently shown to result in embryonic defects/lethality in zebrafish (Kapp et al 2013). Focusing specifically on the brain, depletion of Integrator subunits is associated with excess immature neuroblasts in Drosophila (Zhang et al 2019) and cortical neuron migration defects in mice (van den Berg et al 2017). Recent work has even extended these observations to humans as six individuals with severe neurodevelopmental delay have been shown to carry biallelic mutations in Integrator subunits (Oegema et al 2017).…”

Section: The Integrator Complex Is Critical For Proper Development Pmentioning

confidence: 99%

Attenuation of Eukaryotic Protein-Coding Gene Expression via Premature Transcription Termination

Tatomer

Wilusz

2019

Cold Spring Harb Symp Quant Biol

View full text Add to dashboard Cite

A complex network of RNA transcripts is generated from eukaryotic genomes, many of which are processed in unexpected ways. Here, we highlight how premature transcription termination events at protein-coding gene loci can simultaneously lead to the generation of short RNAs and attenuate production of full-length mRNA transcripts. We recently showed that the Integrator (Int) complex can be selectively recruited to protein-coding gene loci, including Drosophila metallothionein A (MtnA), where the IntS11 RNA endonuclease cleaves nascent transcripts near their 5′ ends. Such premature termination events catalyzed by Integrator can repress the expression of some full-length mRNAs by more than 100-fold. Transcription at small nuclear RNA (snRNA) loci is likewise terminated by Integrator cleavage, but protein-coding and snRNA gene loci have notably distinct dependencies on Integrator subunits. Additional mechanisms that attenuate eukaryotic gene outputs via premature termination have been discovered, including by the cleavage and polyadenylation machinery in a manner controlled by U1 snRNP. These mechanisms appear to function broadly across the transcriptome. This suggests that synthesis of full-length transcripts is not always the default option and that premature termination events can lead to a variety of transcripts, some of which may have important and unexpected biological functions.

show abstract

“…1b, Appendix S1). 37 Mutations in the NIPBL gene, coding for Cohesin Loading Factor involved cortical neuronal migration, 38 cause Cornelia de Lange syndrome 1. The novel missense variant identified in the pedigree G (chr5:37010263), segregating with BD would result in substitution of polar amino acid glutamine by a hydrophobic amino acid proline.…”

Section: Sample Characteristicsmentioning

confidence: 99%

Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes

Ganesh

Pallikonda

Nadella

et al. 2018

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Aim Severe mental illnesses (SMI), such as bipolar disorder and schizophrenia, are highly heritable, and have a complex pattern of inheritance. Genome‐wide association studies detect a part of the heritability, which can be attributed to common genetic variation. Examination of rare variants with next‐generation sequencing may add to the understanding of the genetic architecture of SMI. Methods We analyzed 32 ill subjects from eight multiplex families and 33 healthy individuals using whole‐exome sequencing. Prioritized variants were selected by a three‐step filtering process, which included: deleteriousness by five in silico algorithms; sharing within families by affected individuals; rarity in South Asian sample estimated using the Exome Aggregation Consortium data; and complete absence of these variants in control individuals from the same gene pool. Results We identified 42 rare, non‐synonymous deleterious variants (~5 per pedigree) in this study. None of the variants were shared across families, indicating a ‘private’ mutational profile. Twenty (47.6%) of the variant harboring genes were previously reported to contribute to the risk of diverse neuropsychiatric syndromes, nine (21.4%) of which were of Mendelian inheritance. These included genes carrying novel deleterious variants, such as the GRM1 gene implicated in spinocerebellar ataxia 44 and the NIPBL gene implicated in Cornelia de Lange syndrome. Conclusion Next‐generation sequencing approaches in family‐based studies are useful to identify novel and rare variants in genes for complex disorders like SMI. The findings of the study suggest a potential phenotypic burden of rare variants in Mendelian disease genes, indicating pleiotropic effects in the etiology of SMI.

show abstract

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Cited by 66 publications

References 67 publications

Scc2/Nipbl hops between chromosomal cohesin rings after loading

Scc2/Nipbl hops between chromosomal cohesin rings after loading

Attenuation of Eukaryotic Protein-Coding Gene Expression via Premature Transcription Termination

Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes

Contact Info

Product

Resources

About