The AP-1 family of transcription factors are important regulators of gene expression within Leydig cells

Nguyen, Ha Tuyen; Najih, Mustapha; Martin, Luc J.

doi:10.1007/s12020-021-02888-7

Cited by 10 publications

(7 citation statements)

References 133 publications

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“…The DNA sequence recognized by AP-1 members differs according to the dimer involved. JUN : JUN and FOS : JUN dimers recognize the TPA-response element (TRE; TGA(C/G)TCA) and the cAMP-responsive element (CRE; TGACGTCA), whereas ATF dimers preferentially recognize the CRE motif, and MAF dimers bind to MAF recognition elements (MAREs), a long palindromic sequence that contains TRE or CRE motifs ( 55 ) [reviewed in ( 56 )].…”

Section: Superclass Of Basic Domainsmentioning

confidence: 99%

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Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

2022

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Cell differentiation and acquisition of specialized functions are inherent steps in events that lead to normal tissue development and function. These processes require accurate temporal, tissue, and cell-specific activation or repression of gene transcription. This is achieved by complex interactions between transcription factors that form a unique combinatorial code in each specialized cell type and in response to different physiological signals. Transcription factors typically act by binding to short, nucleotide-specific DNA sequences located in the promoter region of target genes. In males, Leydig cells play a crucial role in sex differentiation, health, and reproductive function from embryonic life to adulthood. To better understand the molecular mechanisms regulating Leydig cell differentiation and function, several transcription factors important to Leydig cells have been identified, including some previously unknown to this specialized cell type. This mini review summarizes the current knowledge on transcription factors in fetal and adult Leydig cells, describing their roles and mechanisms of action.

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Section: Superclass Of Basic Domainsmentioning

confidence: 99%

“…For example, the combination of either FOSL2 or cFOS with cJUN inhibits the stimulatory effect of cJUN on the Star promoter ( 6 , 10 , 59 ). AP-1 factors in Leydig cells have been reviewed elsewhere ( 56 ).…”

Section: Superclass Of Basic Domainsmentioning

confidence: 99%

Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

2022

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“…In silico analysis of the sequences in mutants M3 and M4 predicts that they could be recognized by members of the AP1 and AP2 families. Several AP1 members are known to be present in Leydig cells, including cJUN, a well-characterized activator of several genes (reviewed in [ 28 ]). We, therefore, tested whether members of these families could activate the Insl3 promoter in MA-10 Leydig cells.…”

Section: Resultsmentioning

confidence: 99%

A 35-bp Conserved Region Is Crucial for Insl3 Promoter Activity in Mouse MA-10 Leydig Cells

Giner

Pierre

Robert

et al. 2022

IJMS

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The peptide hormone insulin-like 3 (INSL3) is produced almost exclusively by Leydig cells of the male gonad. INSL3 has several functions such as fetal testis descent and bone metabolism in adults. Insl3 gene expression in Leydig cells is not hormonally regulated but rather is constitutively expressed. The regulatory region of the Insl3 gene has been described in various species; moreover, functional studies have revealed that the Insl3 promoter is regulated by various transcription factors that include the nuclear receptors AR, NUR77, COUP-TFII, LRH1, and SF1, as well as the Krüppel-like factor KLF6. However, these transcription factors are also found in several tissues that do not express Insl3, indicating that other, yet unidentified factors, must be involved to drive Insl3 expression specifically in Leydig cells. Through a fine functional promoter analysis, we have identified a 35-bp region that is responsible for conferring 70% of the activity of the mouse Insl3 promoter in Leydig cells. All tri- and dinucleotide mutations introduced dramatically reduced Insl3 promoter activity, indicating that the entire 35-bp sequence is required. Nuclear proteins from MA-10 Leydig cells bound specifically to the 35-bp region. The 35-bp sequence contains GC- and GA-rich motifs as well as potential binding elements for members of the CREB, C/EBP, AP1, AP2, and NF-κB families. The Insl3 promoter was indeed activated 2-fold by NF-κB p50 but not by other transcription factors tested. These results help to further define the regulation of Insl3 gene transcription in Leydig cells.

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“…Among these, KLF3, MyoD, and FoxP1 act as transcription repressors and rest are transcription activators. AP1 is a family of transcription factors that is subdivided into Fos and Jun subfamilies [ 77 ]. PRKCE UTR variants specifically introduce cFos and cJun binding sites at 5'UTR.…”

Section: Discussionmentioning

confidence: 99%

PRKCE non-coding variants influence on transcription as well as translation of its gene

et al. 2022

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Untranslated regions of the gene play a crucial role in gene expression regulation at mRNA and protein levels. Mutations at UTRs impact expression by altering transcription factor binding, transcriptional/translational efficacy, miRNA-mediated gene regulation, mRNA secondary structure, ribosomal translocation, and stability. PKCε, a serine/threonine kinase, is aberrantly expressed in numerous diseases such as cardiovascular disorders, neurological disorders, and cancers; its probable cause is unknown. Therefore, in the current study, the influence of PRKCE 5’-and 3'UTR variants was explored for their potential impact on its transcription and translation through several bioinformatics approaches. UTR variants data was obtained through different databases and initially evaluated for their regulatory function. Variants with regulatory function were then studied for their effect on PRKCE binding with transcription factors (TF) and miRNAs, as well as their impact on mRNA secondary structure. Study outcomes indicated the regulatory function of 73 5'UTR and 17 3'UTR variants out of 376. 5'UTR variants introduced AP1 binding sites and promoted the PRKCE transcription. Four 3'UTR variants introduced a circular secondary structure, increasing PRKCE translational efficacy. A region in 5'UTR position 45,651,564 to 45,651,644 was found where variants readily influenced the miRNA-PRKCE mRNA binding. The study further highlighted a PKCε-regulated feedback loop mechanism that induces the activity of TFs, promoting its gene transcription. The study provides foundations for experimentation to understand these variants’ role in diseases. These variants can also serve as the genetic markers for different diseases’ diagnoses after validation at the cell and population levels.

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The AP-1 family of transcription factors are important regulators of gene expression within Leydig cells

Cited by 10 publications

References 133 publications

Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

A 35-bp Conserved Region Is Crucial for Insl3 Promoter Activity in Mouse MA-10 Leydig Cells

PRKCE non-coding variants influence on transcription as well as translation of its gene

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