HNF4 Regulates Fatty Acid Oxidation and Is Required for Renewal of Intestinal Stem Cells in Mice

Chen, Lei; Vasoya, Roshan P.; Toke, Natalie H.; Parthasarathy, Aditya; Luo, Shirley; Chiles, Eric; Flores, Juan; Gao, Nan; Bonder, Edward M.; Su, Xiaoyang; Verzi, Michael P.

doi:10.1053/j.gastro.2019.11.031

Cited by 135 publications

(141 citation statements)

References 66 publications

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“…HNF4A knockout in mouse intestinal epithelium hampered the formation of regenerative foci following lethal irradiation, in line with HNF4A being required for intestinal regeneration [ 66 ]. Consistently, HNF4 factors in the intestine were observed to promote lipid oxidation and renewal of intestinal stem cells [ 105 ]. Altogether, re-expression of HNF4 and associated identity TF networks after initial decrease is crucial for re-establishment of identity gene expression, and hence restoration of organ function.…”

Section: Hnf4 Loss Contributes To Loss Of Identity In Diseasementioning

confidence: 87%

“…Interaction with the TATA-Box Binding Protein Associated Factor 4 (TAF4) subunit of the general transcription factor IID (TFIID), a member of the transcription preinitiation complex, stabilizes HNF4A occupancy of promoters [ 104 ] where it facilitates recruitment of RNA Polymerase II (POLR2) [ 73 ]. A fraction of HNF4 promoter-bound genes are involved in housekeeping functions, probably more related to the requirement for cell-specific control of cellular homeostasis including HNF4-mediated regulation of cell proliferation in hepatocytes or intestinal cells [ 57 , 59 , 64 , 65 , 105 ]. At liver identity genes, HNF4A recruitment to enhancers, organized into super-enhancers, add up to promoter binding [ 7 ].…”

Section: Mechanisms Of Action In the Control Of Cell Identity By Hmentioning

confidence: 99%

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Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology

Dubois

Staels

Lefèbvre

et al. 2020

Cells

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Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor (TF) belonging to the nuclear receptor family whose expression and activities are restricted to a limited number of organs including the liver and gastrointestinal tract. In this review, we present robust evidence pointing to HNF4 as a master regulator of cellular differentiation during development and a safekeeper of acquired cell identity in adult organs. Importantly, we discuss that transient loss of HNF4 may represent a protective mechanism upon acute organ injury, while prolonged impairment of HNF4 activities could contribute to organ dysfunction. In this context, we describe in detail mechanisms involved in the pathophysiological control of cell identity by HNF4, including how HNF4 works as part of cell-specific TF networks and how its expression/activities are disrupted in injured organs.

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Section: Hnf4 Loss Contributes To Loss Of Identity In Diseasementioning

confidence: 87%

Section: Mechanisms Of Action In the Control Of Cell Identity By Hmentioning

confidence: 99%

Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology

Dubois

Staels

Lefèbvre

et al. 2020

Cells

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“…Similar to HNF1α, HNF4α contains a POU domain consisting of zinc finger regions that allow for DNA binding ( Figure 3D) [228]. HNF4α is associated with lipid and carbohydrate metabolism, inflammation as well as embryogenesis [229][230][231][232]. Although found in other cell types, HNF4α is expressed in hepatocytes and is upregulated upon HBV infection [233].…”

Section: Hepatocyte Nuclear Factor 4αmentioning

confidence: 99%

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

Turton

Meier-Stephenson

Badmalia

et al. 2020

Viruses

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The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA (cccDNA) that resides in the nucleus. As HBV replication requires the help of host transcription factors to replicate, focusing on host protein–HBV genome interactions may reveal insights into new drug targets against cccDNA. The structural details on such complexes, however, remain poorly defined. In this review, the current literature regarding host transcription factors’ interactions with HBV cccDNA is discussed.

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“…MODY . Animal models have been generated using CRISPR-Cas9 technology to study features of HNF4A ( 232 ), as well as a GCK mutant rabbit model exhibiting many features of HNF4A ( 233 ) and INS mutant piglets which are insulin-deficient ( 161 ). Similarly, a CRISPR-Cas9 nuclease was used to create the MODY gene reporter through homologous recombination, such as PDX1-eGFP reporter ( 234 ).…”

Section: Application Of Genome Editing To Disease-relevant Genetic mentioning

confidence: 99%

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research

Cherkaoui

Misra

et al. 2020

Front. Endocrinol.

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The inheritance of variants that lead to coding changes in, or the mis-expression of, genes critical to pancreatic beta cell function can lead to alterations in insulin secretion and increase the risk of both type 1 and type 2 diabetes. Recently developed clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) gene editing tools provide a powerful means of understanding the impact of identified variants on cell function, growth, and survival and might ultimately provide a means, most likely after the transplantation of genetically “corrected” cells, of treating the disease. Here, we review some of the disease-associated genes and variants whose roles have been probed up to now. Next, we survey recent exciting developments in CRISPR/Cas9 technology and their possible exploitation for β cell functional genomics. Finally, we will provide a perspective as to how CRISPR/Cas9 technology may find clinical application in patients with diabetes.

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HNF4 Regulates Fatty Acid Oxidation and Is Required for Renewal of Intestinal Stem Cells in Mice

Cited by 135 publications

References 66 publications

Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology

Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research

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