NIPBL (Nipped-B Like) is the primary cohesin loading factor, essential for the deposition of the cohesin complex onto chromatin. Named after the Drosophila Nipped-B gene, NIPBL mutations cause the majority of Cornelia de Lange syndrome (CdLS) cases, a multisystem developmental disorder with significant neurological manifestations[@krantz2004]. Beyond cohesin loading, NIPBL regulates gene expression programs critical for neurodevelopment and brain function.
NIPBL (Nipped-B Like) is the primary cohesin loading factor, essential for the deposition of the cohesin complex onto chromatin. Named after the Drosophila Nipped-B gene, NIPBL mutations cause the majority of Cornelia de Lange syndrome (CdLS) cases, a multisystem developmental disorder with significant neurological manifestations[@krantz2004]. Beyond cohesin loading, NIPBL regulates gene expression programs critical for neurodevelopment and brain function.
Function
Cohesin Loading Mechanism
NIPBL, together with its partner MAU2, forms the cohesin loader complex that:
Opens the cohesin ring at the SMC3-RAD21 interface
Topologically entraps chromosomal DNA
Positions cohesin at specific genomic loci marked by CTCF and transcription factors[@higashi2020]
This loading is ATP-dependent and requires the SMC1A-SMC3 ATPase head domains.
[Krantz ID, et al, Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B (2004)](https://doi.org/10.1038/ng1364)
[Higashi TL, et al, A structure-based mechanism for cohesin loading onto chromosomes (2020)](https://doi.org/10.1038/s41586-019-1873-1)
[Kagey MH, et al, Mediator and cohesin connect gene expression and chromatin architecture (2010)](https://doi.org/10.1038/nature09380)
[Dorsett D, Strom L, The ancient and evolving roles of cohesin in gene expression and DNA repair (2012)](https://doi.org/10.1016/j.cub.2012.02.046)
[Watrin E, Peters JM, The cohesin complex is required for the DNA damage-induced G2/M checkpoint (2006)](https://doi.org/10.1016/j.molcel.2006.07.018)
[Tonkin ET, et al, NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome (2004)](https://doi.org/10.1038/ng1363)
[Oliver C, et al, Cornelia de Lange syndrome: extending the physical and psychological phenotype (2008)](https://doi.org/10.1002/ajmg.a.32247)
[Kon A, et al, Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms (2013)](https://doi.org/10.1038/ng.2731)
[Merckenschlager M, Odom DT, CTCF and cohesin: linking gene regulatory elements with disease genes (2013)](https://doi.org/10.1016/j.cell.2013.02.029)
[Kline AD, et al, Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement (2018)](https://doi.org/10.1038/s41576-018-0036-0)