Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

Butyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential...

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Main Authors: Clarissa Boschiero, Yahui Gao, Ransom L. Baldwin, Li Ma, Cong-jun Li, George E. Liu
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/9/1177
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author Clarissa Boschiero
Yahui Gao
Ransom L. Baldwin
Li Ma
Cong-jun Li
George E. Liu
author_facet Clarissa Boschiero
Yahui Gao
Ransom L. Baldwin
Li Ma
Cong-jun Li
George E. Liu
author_sort Clarissa Boschiero
collection DOAJ
description Butyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential roles in chromatin organization and gene expression regulation. Although CTCF-binding sites have been identified recently in cattle, a deeper characterization, including differentially CTCF-binding sites (DCBS), is vital for a better understanding of butyrate’s role in the chromatin landscape. This study aimed to identify CTCF-binding regions and DCBS under a butyrate-induced condition using ChIP-seq in bovine cells; 61,915 CTCF peaks were identified in the butyrate and 51,347 in the control. From these regions, 2265 DCBS were obtained for the butyrate vs. control comparison, comprising ~90% of induced sites. Most of the butyrate DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment showed crucial terms for the induced DCBS, mainly related to cellular proliferation, cell adhesion, and growth regulation. Interestingly, the ECM-receptor interaction pathway was observed for the induced DCBS. Motif enrichment analysis further identified transcription factors, including CTCF, BORIS, TGIF2, and ZIC3. When DCBS was integrated with RNA-seq data, putative genes were identified for the repressed DCBS, including <i>GATA4</i>. Our study revealed promising candidate genes in bovine cells by a butyrate-induced condition that might be related to the regulation of rumen development, such as integrins, keratins, and collagens. These results provide a better understanding of the function of butyrate in cattle rumen development and chromatin landscape regulation.
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spelling doaj.art-68f3983626eb4503891645cdc6a410b82023-11-23T15:14:10ZengMDPI AGBiomolecules2218-273X2022-08-01129117710.3390/biom12091177Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle CellsClarissa Boschiero0Yahui Gao1Ransom L. Baldwin2Li Ma3Cong-jun Li4George E. Liu5Animal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USAAnimal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USAAnimal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USADepartment of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USAAnimal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USAAnimal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USAButyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential roles in chromatin organization and gene expression regulation. Although CTCF-binding sites have been identified recently in cattle, a deeper characterization, including differentially CTCF-binding sites (DCBS), is vital for a better understanding of butyrate’s role in the chromatin landscape. This study aimed to identify CTCF-binding regions and DCBS under a butyrate-induced condition using ChIP-seq in bovine cells; 61,915 CTCF peaks were identified in the butyrate and 51,347 in the control. From these regions, 2265 DCBS were obtained for the butyrate vs. control comparison, comprising ~90% of induced sites. Most of the butyrate DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment showed crucial terms for the induced DCBS, mainly related to cellular proliferation, cell adhesion, and growth regulation. Interestingly, the ECM-receptor interaction pathway was observed for the induced DCBS. Motif enrichment analysis further identified transcription factors, including CTCF, BORIS, TGIF2, and ZIC3. When DCBS was integrated with RNA-seq data, putative genes were identified for the repressed DCBS, including <i>GATA4</i>. Our study revealed promising candidate genes in bovine cells by a butyrate-induced condition that might be related to the regulation of rumen development, such as integrins, keratins, and collagens. These results provide a better understanding of the function of butyrate in cattle rumen development and chromatin landscape regulation.https://www.mdpi.com/2218-273X/12/9/1177CTCFcattlebutyratedifferentially CTCF-binding sitesMDBK cells
spellingShingle Clarissa Boschiero
Yahui Gao
Ransom L. Baldwin
Li Ma
Cong-jun Li
George E. Liu
Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
Biomolecules
CTCF
cattle
butyrate
differentially CTCF-binding sites
MDBK cells
title Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
title_full Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
title_fullStr Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
title_full_unstemmed Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
title_short Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells
title_sort butyrate induces modifications of the ctcf binding landscape in cattle cells
topic CTCF
cattle
butyrate
differentially CTCF-binding sites
MDBK cells
url https://www.mdpi.com/2218-273X/12/9/1177
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