There are about 30 proteins in the nucleoporin family, and they carry out a number of different functions in addition to forming the nuclear pore. Several of them are known to act as transcription factors: This means they help to regulate when and how genes get translated into proteins.
In a new finding, a team of investigators has uncovered in mouse cells a previously unknown job for a protein called nup98. In addition to helping control the movement of molecules in and out of the nucleus of the cell, they found that it also helps direct the development of blood cells, enabling immature blood stem cells to differentiate into many specialized mature cell types. Further, they discovered the mechanism by which--when perturbed--this differentiation process can contribute to the formation of certain types of leukemia. The findings are published in Genes & Development.
Nup98 binds predominantly to transcription start sites to recruit the Wdr82–Set1A/COMPASS (complex of proteins associated with Set1) complex, which is required for deposition of the histone 3 Lys4 trimethyl (H3K4me3)-activating mark.
Depletion of Nup98 or Wdr82 abolishes Set1A recruitment to chromatin and subsequently ablates H3K4me3 at adjacent promoters. Furthermore, expression of a Nup98 fusion protein implicated in aggressive AML causes mislocalization of H3K4me3 at abnormal regions and up-regulation of associated genes.
The finding that nup98 has this additional function was not entirely unexpected. Earlier research from lab had found that it plays a role in gene regulation in other cell types. But the team didn't know about its function in hematopoietic (blood) cells.
In addition, until now the mechanism of how nup98 regulates transcription was not known. The investigators found that it acts through a link with a protein complex called Wdr82-Set1/COMPASS, which is part of the cell's epigenetic machinery. "This epigenetic process helps to control when genes are transcribed into proteins and when transcription is blocked," says the senior author.
Another thing that was different about this study is that it was done in mouse cells rather than simpler model organisms like yeast and fruit flies. "This is the first mechanistic insight of how one of these nup proteins works in mammals," senior author adds. "We have only touched the surface here in uncovering how this evolutionarily conserved mechanism works in mammalian cells." Future work in his lab will extend the study of nup98 to primates and humans.
https://www.salk.edu/news-release/multifunctional-protein-contributes-blood-cell-development/
http://genesdev.cshlp.org/content/early/2017/12/21/gad.306753.117.abstract
Latest News
Neurons wreak havoc on meta…
By newseditor
Posted 01 May
Colorectal oncogenesis in m…
By newseditor
Posted 01 May
Antisense oligonucleotide t…
By newseditor
Posted 01 May
The cellular mechanisms of…
By newseditor
Posted 30 Apr
X-chromosome inactivation m…
By newseditor
Posted 30 Apr
Other Top Stories
Low-protein high-carb diet shows promise for healthy brain aging
Read more
Effects of early education intervention on behavior persist for 4 d…
Read more
Helios, a key transcriptional regulator implicated in age-related h…
Read more
Somatic APP gene recombination in Alzheimer's disease and normal ne…
Read more
Probiotics is no help to children with acute intestinal infections
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Genomic and non-genomic act…
By newseditor
Posted 01 May
a2d1-mediated maladaptive s…
By newseditor
Posted 01 May
Neuron-astrocyte metabolic…
By newseditor
Posted 01 May
Spatiotemporally resolved c…
By newseditor
Posted 01 May
A team of chaperones play t…
By newseditor
Posted 01 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar