Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue

Patel, Bhavin V.; Yao, Fanrong; Howenstine, Aidan; Takenaka, Risa; Hyatt, Jacob A.; Sears, Karen E.; Shewchuk, Brian M.

doi:10.1016/j.jmb.2020.09.022

Cited by 6 publications

(6 citation statements)

References 76 publications

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“…This suggests that intragenic enhancer chromatin from ITGAD and ZNF843 upregulated the adjacent COX6A2 rather than ITGAD and ZNF843 [ 23 ]. The gene neighbors (5′-to-3′) CPT1B and CHKB displayed an inverse correlation between their expression in most tissues, including SkM and heart, unlike a previous report about five mouse tissues [ 66 ]. Myoblasts express mostly just CHKB (which fosters formation of the inner mitochondrial membrane) while ESC cells predominantly express the read-through CHKB-CPT1B transcript initiated at the CHKB promoter ( Figure 4 ).…”

Section: Discussioncontrasting

confidence: 78%

“…In contrast, SkM and heart express much more CPT1B (essential for fatty acid oxidation and contributing to ATP synthesis) but still have considerable levels of CHKB RNA ( Figure 4 D,E). We propose that a highly active CPT1B promoter in striated muscle inhibits read-through transcription from the upstream CHKB gene and downmodulates CHKB promoter activity but still allows production of enough mRNA from both genes for their critical roles in skeletal muscle and heart [ 30 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

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Epigenetics of Mitochondria-Associated Genes in Striated Muscle

2021

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Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated with striated muscle and mitochondria. Many showed strong correlations between their tissue-specific transcription levels, and their tissue-specific promoter, enhancer, or open chromatin as well as their DNA hypomethylation. Their striated muscle-specific enhancer chromatin was inside, upstream, or downstream of the gene, throughout much of the gene as a super-enhancer (CKMT2, SLC25A4, and ACO2), or even overlapping a neighboring gene (COX6A2, COX7A1, and COQ10A). Surprisingly, the 3′ end of the 1.38 Mb PRKN (PARK2) gene (involved in mitophagy and linked to juvenile Parkinson’s disease) displayed skeletal muscle/myoblast-specific enhancer chromatin, a myoblast-specific antisense RNA, as well as brain-specific enhancer chromatin. We also found novel tissue-specific RNAs in brain and embryonic stem cells within PPARGC1A (PGC-1α), which encodes a master transcriptional coregulator for mitochondrial formation and metabolism. The tissue specificity of this gene’s four alternative promoters, including a muscle-associated promoter, correlated with nearby enhancer chromatin and open chromatin. Our in-depth epigenetic examination of these genes revealed previously undescribed tissue-specific enhancer chromatin, intragenic promoters, regions of DNA hypomethylation, and intragenic noncoding RNAs that give new insights into transcription control for this medically important set of genes.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Epigenetics of Mitochondria-Associated Genes in Striated Muscle

2021

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“…Carnitine palmitoyl transferase 1B ( CPT1B ) is closely related to choline kinase β (CHKB). The CHKB gene is transcribed from the same DNA strand and terminates upstream of CPT1B ( 36 ). The tight combination of CHKB - CPT1B may overlap the cis-action regulatory domains and realise a common regulatory mechanism ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple databases analyzed the prognosis prediction of renin secretion pathway-related genes in renal clear cell carcinoma and immunotherapy

Li,

Bao,

Xiao

et al. 2024

Transl Cancer Res

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Background Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour and its progression is associated with the renin secretion pathway, so this study aimed to develop a prognostic model based on renin secretion pathway-related genes. Methods First, 453 renin secretion pathway-related genes were acquired [|log fold change (FC)| >1.5, false discovery rate (FDR) <0.05] from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The data were combined and further screened for 188 genes associated with ccRCC prognosis (P<0.05) by univariate independent prognostic analysis. These genes were subjected to least absolute shrinkage and selection operator regression to identify potential prognostic genes to construct the prognostic model. The stability of the model was externally validated. Combined risk scores and clinical information were used to create nomograms to accurately reflect patient survival. The model-related genes were further mined for subsequent analysis. Results A prognostic model of six renin secretion pathway genes ( IGFBP3 , PLAUR , CHKB-CPT1B , HOXA13 , CDH13 , and CDC20 ) was developed. Its reliability in predicting disease prognosis was confirmed by survival analysis, receiver operating characteristic (ROC) curve analysis and a risk curve. The nomogram and calibration curve showed good accuracy. The immune-related analyses revealed that the low-risk group would benefit more from immunotherapy. Conclusions The prognostic model of ccRCC based on six renin secretion pathway-related genes can be used to guide the precise treatment of ccRCC patients.

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“…CPT1B gene plays a vital role in regulating fat decomposition and energy supply. Studies have shown that CPT1B is of great significance to the development of brown adipose tissue [ 24 ]. Moreover, in bovine fetal fibroblasts, changes in triglyceride content were related to the expression level of CPT1B [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

miR-27a Regulates Sheep Adipocyte Differentiation by Targeting CPT1B Gene

Huang

Yang

et al. 2021

Animals

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MiRNAs are vital regulators and play a major role in cell differentiation, biological development, and disease occurrence. In recent years, many studies have found that miRNAs are involved in the proliferation and differentiation of adipocytes. The objective of this study was to evaluate the effect of miR-27a and its target gene CPT1B on ovine preadipocytes differentiation in Small-tailed Han sheep (Ovis aries). Down-regulation of miR-27a significantly promoted the production of lipid droplets, while overexpression of miR-27a led to a reduction in lipid droplet production. In addition, inhibition of miR-27a led to a significant increase in the expression of genes involved in lipid synthesis, including PPAR γ, SCD, LPL, and FABP4. Target Scan software predicted that CPT1B is a new potential target gene of miR-27a. Further experiments revealed that CPT1B gene expression and protein levels were negatively correlated with miR-27a expression. Overexpression of miR-27a led to a significant decrease in CPT1B mRNA levels and inhibited the accumulation of lipid droplets and vice versa. Moreover, overexpression of CPT1B promoted the synthesis of lipid droplets in ovine preadipocytes. Furthermore, luciferase reporter assays confirmed CPT1B to be a miR-27a direct target gene. This study confirmed that miR-27a increases the expression of genes related to lipid synthesis in ovine preadipocytes by targeting CPT1B, thereby promoting the synthesis of lipid droplets. The results of this study can be used to be exploited in devising novel approaches for improving the IMF content of sheep.

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Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue

Cited by 6 publications

References 76 publications

Epigenetics of Mitochondria-Associated Genes in Striated Muscle

Epigenetics of Mitochondria-Associated Genes in Striated Muscle

Multiple databases analyzed the prognosis prediction of renin secretion pathway-related genes in renal clear cell carcinoma and immunotherapy

miR-27a Regulates Sheep Adipocyte Differentiation by Targeting CPT1B Gene

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