Evidence map›Paper›PMID 38768033›Full record

ArticleCell reports2024

Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.

Kiranmayi Vemuri, Sneha Kumar, Lei Chen, Michael P Verzi

Abstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Kiranmayi VemuriDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Sneha KumarDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Lei ChenSchool of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
Michael P VerziDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition & Health, Rutgers University, New Brunswick, NJ 08901, USA; NIEHS Center for Environmental Exposures and Disease (CEED), Rutgers EOHSI, Piscataway, NJ 08854, USA. Electronic address: verzi@biology.rutgers.edu.

Funding

Mechanisms Driving Metabolic Shifts in the Intestinal EpitheliumR01DK126446 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI VERZI, MICHAEL P. · 2021 to 2025
$2.1M
Mechanisms of Intestinal Epithelial DifferentiationR01DK121915 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ELLISON, CHRISTOPHER EUGENE, VERZI, MICHAEL P. · 2020 to 2023
$1.7M
NIDDK NIH HHS R01 DK121915NIDDK NIH HHS R01 DK126446
6 · The paper itself

Abstract

Terminal differentiation requires massive restructuring of the transcriptome. During intestinal differentiation, the expression patterns of nearly 4,000 genes are altered as cells transition from progenitor cells in crypts to differentiated cells in villi. We identify dynamic occupancy of RNA polymerase II (Pol II) to gene promoters as the primary driver of transcriptomic shifts during intestinal differentiation in vivo. Changes in enhancer-promoter looping interactions accompany dynamic Pol II occupancy and are dependent upon HNF4, a pro-differentiation transcription factor. Using genetic loss-of-function, chromatin immunoprecipitation sequencing (ChIP-seq), and immunoprecipitation (IP) mass spectrometry, we demonstrate that HNF4 collaborates with chromatin remodelers and loop-stabilizing proteins and facilitates Pol II occupancy at hundreds of genes pivotal to differentiation. We also explore alternate mechanisms that drive differentiation gene expression and find that pause-release of Pol II and post-transcriptional mRNA stability regulate smaller subsets of differentially expressed genes. These studies provide insights into the mechanisms of differentiation in renewing adult tissue.

Indexed as

Cell DifferentiationHepatocyte Nuclear Factor 4RNA Polymerase IIAnimalsEnhancer Elements, GeneticIntestinesMicePromoter Regions, GeneticHepatocyte Nuclear Factor 4Hnf4a protein, mouseRNA Polymerase IIchromatin loopingCP: GenomicsCP: Molecular biologycrypt-villus axisdynamic Pol II occupancyHNF4 transcription factorsintestinal epitheliumPol II ChIP-seqpost-transcriptional gene regulationpromoter-proximal pausingrapid immunoprecipitation mass spectrometry of endogenous proteinsRNA polymerase II

Identifiers

PMID38768033
PMCPMC11264335

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.