CoChat
Sign Up
Cited by 1,270

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes

Horton, Jay D., Shah, Nila A., Warrington, Janet A., Anderson, Norma N., Park, Sahng Wook, Brown, Michael S., Goldstein, Joseph L.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1534923100
Open this paper in CoChat — free account

Abstract

The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap –/– livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1534923100

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PCSK9 is an important post-translational regulator of LDLR levels that functions to reduce expression of LDLR protein.

    “PCSK9 is an important post-translational regulator of LDLR levels that functions to reduce expression of LDLR protein28,39.”

    From RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels (2023) · cites this paper as [39]

    The Results describe Narc-1 as a serine protease whose human orthologue is associated with hypercholesterolemia, but do not say it reduces LDLR protein. Searches for PCSK9, post-translational regulation, and LDLR protein reduction found no passage establishing the claimed mechanism in our copy. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • SREBPs contain an SRE in their promoter and induce their own expression in a positive feedback mechanism.

    “As SREBPs contain an SRE in their promoter region, they induce their own expression in a positive feedback mechanism4,18.”

    From Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism (2020) · cites this paper as [18]

  • SREBP-2 preferentially regulates expression of genes involved in cholesterol production.

    “SREBP-2 preferentially regulates the expression of genes involved in cholesterol production (Horton et al., 2003).”

    From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Horton et al., 2003

  • In the liver, SREBP1c primarily controls fatty acid synthesis and mobilization, while SREBP2 controls cholesterol biosynthesis and lipoprotein uptake.

    “In the liver, SREBP1c is the prominent SREBP1 isoform and primarily controls fatty acid synthesis and mobilization, while SREBP2 controls cholesterol biosynthesis and lipoprotein uptake [12,13].”

    From Loss of the E3 ubiquitin ligase MARCHF6 alters hepatic lipid metabolism and drives spontaneous hepatosteatosis (2026) · cites this paper as [13]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 35

  1. 10.1006/abbi.2001.2615 · DOI · Paper page
  2. 10.1016/S0092-8674(02)00872-3 · DOI · Paper page
  3. 10.1073/pnas.162488899 · DOI · Paper page
  4. 10.1172/JCI2961 · DOI
  5. 10.1172/JCI118951 · DOI
  6. 10.1101/gad.891301 · DOI · Paper page
  7. 10.1016/S1388-1981(00)00140-2 · DOI
  8. 10.1038/15124 · DOI
  9. 10.1073/pnas.0335507100 · DOI · Paper page
  10. 10.1038/ng1161 · DOI · Paper page
  11. 10.1073/pnas.052143799 · DOI · Paper page
  12. 10.1038/75192 · DOI
  13. 10.1016/0014-5793(93)81416-W · DOI
  14. 10.1074/jbc.M304969200 · DOI
  15. 10.1016/S0022-2275(20)30180-2 · DOI
  16. 10.1074/jbc.M300553200 · DOI
  17. 10.1074/jbc.274.46.32725 · DOI
  18. 10.1074/jbc.273.52.35299 · DOI · Paper page
  19. 10.1016/S0167-4781(01)00364-5 · DOI
  20. 10.1126/science.290.5497.1771 · DOI
  21. 10.1074/jbc.M109927200 · DOI
  22. 10.1073/pnas.98.4.1477 · DOI · Paper page
  23. 10.1074/jbc.M207187200 · DOI
  24. 10.1074/jbc.M202394200 · DOI
  25. 10.1006/abbi.2001.2307 · DOI
  26. 10.1073/pnas.252626999 · DOI
  27. Nokelainen, P., Peltoketo, H., Vihko, R. & Vihko, P. (1998) Mol. Endocrinol. 12, 1048–1059.9658408
  28. Misawa K. Horiba T. Arimura N. Hirano Y. Inoue J. Emoto N. Shimano H. Shimizu M. & Sato R. (July 10 2003) J. Biol. Chem. 10.1074/jbc.M302387200. · DOI
  29. 10.1101/gad.844900 · DOI
  30. 10.1074/jbc.M005353200 · DOI · Paper page
  31. 10.1074/jbc.M111041200 · DOI
  32. 10.1161/01.ATV.19.6.1456 · DOI
  33. 10.1210/endo.140.12.7220 · DOI
  34. 10.1074/jbc.M106785200 · DOI
  35. 10.1053/jhep.2003.50193 · DOI

Cited by

Sorted by citations

Metadata

Authors
Horton, J. D., Shah, N. A., Warrington, J. A., Anderson, N. N., Park, S. W., Brown, M. S., & Goldstein, J. L.
Affiliations
Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046; and Affymetrix, Inc., Santa Clara, CA 95051
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-09-25
Volume
100
Issue
21
Pages
12027-12032
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1534923100
Cited by
1,270
References
1
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review