Test Large Dataset Deposit (Proteomics)

[chrisdaaz]

Severity

Is the production site running?

• [x] yes
• [ ] no

Are staff blocked from performing their work?

• [ ] yes
• [x] no

Descriptive summary

This is a dataset from Proteomics we can use for testing, but eventually they want it publicly available (the paper publication is pending peer-review).

• [ ] check max files per work setting
• [ ] import using box
• [ ] create new issues if needed

Data files

Access: https://northwestern.box.com/s/j4fjqx78auc04zfrpnx2aybqayoyka6q

• Total = 64.5 GB
• no. files = 126
• avg. file size = 512 MB
• max file size = 611 MB
• min file size = 410 MB

Work Metadata

Authors: Tao Wang, Matthew V. Holt, Nicolas L. Young

Title: Immediate-Early Histone H4 Proteoform Response Dynamics to SUV4-20 Inhibition

Publish Date: Pending

Publisher: Pending

Keywords: histone methyltransferase; SUV4-20; histone post-translational modifications; epigenetic inhibitor; breast cancer; top down proteomics

Abstract: The dynamics of histone post-translational modifications (PTMs) are sparsely described, especially in their true physiological context of proteoforms (single histone molecules harboring combinations of PTMs). Here we time resolve the response of cells to SUV4-20 methyltransferase inhibition and unbiasedly quantitate the dynamic response of histone H4 PTMs and proteoforms. Contrary to the prevailing dogma, cells exhibit an immediate-early response with changes to histone proteoforms. Cells also recover to basal-like conditions upon removal of epigenetic inhibitors rapidly. Inhibition of SUV4-20 results in decreased H4{K20me2}; however, a marked increase in H4{K20me3} is observed, implying that another enzyme mediates H4K20me3. Most surprisingly, SUV4-20 inhibition results in an increase in histone H4 acetylation attributable specifically to proteoforms containing K20me2. This led us to hypothesize that hyperacetylated proteoforms protect K20me2 from demethylation as an evolved compensatory mechanism. This concept is supported by subsequent results that pretreatment with an HDACi substantially diminishes the effects of SUV4-20 inhibition, and is further confirmed by HATi facilitating SUV4-20 inhibition to decrease discrete {K20me2}. Thus, the chromatin response of cells to sudden perturbations is significantly faster, nuanced and complex than previously described. The persistent nature of chromatin regulation may indeed be achieved by a network of dynamic equilibria with compensatory mechanisms that operate at the proteoform level.

Related work

179

[davidschober]

per @cpd3149 we do not have to retain structure and we can break up fillsets into multiple related works if necessary.y

[kdid]

oh hold waiting for #320

[kdid]

Tested. 23 works to 45 minutes and had over 50% failure rate.