Nature - USA (2020-01-23)

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nature research | reporting summary

April 2018

Data

Policy information about availability of data

All manuscripts must include a data availability statement. This statement should provide the following information, where applicable:

• Accession codes, unique identifiers, or web links for publicly available datasets


• A list of figures that have associated raw data


• A description of any restrictions on data availability
  The raw and processed RNA-seq, ChIP-seq and ATAC-seq data are deposited on GEO (GSE118765 and GSE128958):
  https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118765
  https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE128958
  The following secure token has been created to allow review of record:
  GSE118765: ersrqismjhypxex
  GSE128958: ynupygawfdefdcp

Field-specific reporting

Please select the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences

For a reference copy of the document with all sections, see nature.com/authors/policies/ReportingSummary-flat.pdf

Life sciences study design

All studies must disclose on these points even when the disclosure is negative.

Sample size For high throughput sequencing experiments, two independent biological replicates were used where possible and to strengthen the

conclusions of the study. Sample sized for other assays (qPCR, ChIP-PCR, etc.) were chosen based on our prior experience and common

standards in the field for detecting statistically significant differences between conditions.

Data exclusions No data was excluded from the studies.

Replication All attempts at replication were successful. Biological replicates of each experiment is stated under each figure legend and all attempts were

successful. Moreover, findings were repeatedly reproduced throughout the study: RNA-seq with qRT-PCR in multiple cell lines; protein levels

with Western blot and immunostaining; cell response assays with different cell line models.

Randomization In animal experiments, mice were randomly assigned to each experiment group.

Blinding Investigators were blinded to cell groups and mouse groups when collecting results.

Reporting for specific materials, systems and methods

Materials & experimental systems

n/a Involved in the study

Unique biological materials

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Unique biological materials

Policy information about availability of materials

Obtaining unique materials DNA plasmids: pLVX-Tight-Puro-KrasG12D, pLVX-IRES-Hyg-SMAD4 (Addgene #107128), SGEP (Addgene #111170), pLenti-HA-

Rreb1, pSpCas9(BB)-2A-GFP (PX458) (Addgene #48138), pSpCas9(BB)-2A-Puro (PX459) (Addgene #48139), pLVX-EF1α-IRES-