Involving AP‐2 transcription factor in connexin 26 up‐regulation during pregnancy and lactation

Tu, Zheng Jin; Pan, Weihong; Gong, Zhuo; Kiang, David T.

doi:10.1002/mrd.1002

Cited by 8 publications

(11 citation statements)

References 35 publications

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“…Furthermore, connexin-26 expression is confined to the alveolar epithelium, specifically localized to where adjacent alveolar cells are in contact (Locke et al, 2000). A functional binding site for the AP-2 transcription factors has been identified in the connexin-26 promoter (Tu et al, 2001), indicating that our transcript-profiling experiment may have found at least one transcription factor cascade following PRL binding to its receptor on mammary epithelial cells.…”

Section: Mammary Transcriptional Response To Prlmentioning

confidence: 79%

Investigation of the Transcriptional Changes Underlying Functional Defects in the Mammary Glands of Prolactin Receptor Knockout Mice

Ormandy

Naylor²,

Harris³

et al. 2003

Recent Progress in Hormone Research

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Knockout (KO) mice have been created that carry null mutations of genes encoding molecules essential for prolactin (PRL) release, PRL, the receptor for prolactin (PRLR), and various members of the receptor's signaling pathway. This allowed an in vivo genetic analysis of the role of PRL in target organ function. In PRLKO and PRLRKO mice, mammary ductal side branching was absent, terminal end bud (TEB)-like structures persisted at the ductal termini well into maturity, and no alveolar buds formed along the ductal tree. Transplants of recombined mammary glands formed from stromal and epithelial elements with and without PRLR showed normal development, while supplementation of progesterone levels in PRLKO animals restored ductal side branching. During pregnancy, PRLR heterozygous animals initially showed normal ductal and alveolar development. However, alveolar development stalled during late pregnancy, preventing successful lactation. This defect could be rescued by the loss of a single allele of the suppressor of cytokine signaling (SOCS) 1 gene. Transplants of recombined glands containing PRLRKO epithelium and wild-type (WT) stroma formed alveolar buds during pregnancy but showed no lobuloalveolar development. Recombinations of WT epithelium and PRLRKO stroma showed normal development, demonstrating that a direct action of the lactogenic hormones is confined to the epithelium, to promote lobuloalveolar development. Transcript profiling of epithelial transplants expressing or not expressing PRLR was used during early pregnancy to investigate the transcriptional response to lactogens underlying this defect. Such profiling has identified a number of genes with well-characterized roles in mammary development, in addition to a number of novel transcripts.

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Section: Mammary Transcriptional Response To Prlmentioning

confidence: 79%

Investigation of the Transcriptional Changes Underlying Functional Defects in the Mammary Glands of Prolactin Receptor Knockout Mice

Ormandy

Naylor²,

Harris³

et al. 2003

Recent Progress in Hormone Research

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“…Overexpression of Nkx2.5, a member of the NK2 homeodomain proteins was associated with a decrease in Cx43 expression, suggesting that Nkx2.5 may function as a transcriptional repressor (52). SP1 has also been found involved in the transcriptional regulation of Cx26, in rat mammary gland and uterus, as well as in the activation of Cx40 and Cx32 proximal promoter (53)(54)(55). Moreover, it has been demonstrate that Sox10, a transcription modulator, activates Cx32 expression (56).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Martín

Tawadros

Meylan

et al. 2003

Journal of Biological Chemistry

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Adjacent cells share ions, second messengers, small metabolites, and signaling molecules with a weight as high as 1000 Da (1) through intercellular channels that form gap junctions. This type of intercellular communication permits coordinated cellular activity and allows cells to review the functional state of their neighbors, a critical feature for the homeostasis of multicellular organisms (1-4). Intercellular channels result from the association of two half-channels named connexons, which are contributed to separately by each of two adjacent cells. Each connexon is an assembly of membrane proteins named connexins, which are encoded by a gene family consisting of at least 20 members (5, 6).It has been reported that Cx36 1 is the predominantly expressed connexin in rodent neuronal cells (7-9). Immunogold labeling using freeze-fracture replicas have shown that Cx36 was found only in neurons (10) and indicate that the specific expression of connexins by the different cell types of the nervous system may define separate pathways for neuronal versus glial gap junction communication (10 -12). We recently found that Cx36 is the predominant if not the sole connexin isoform expressed in insulin-producing ␤-cells of rat and mouse pancreatic islets (13,14). Recently, Cx36 content was modified in insulin-secreting cells by using an adenoviral gene transfer approach (15) or a lentivirus-mediated transduction of cx36 cDNA (16) in order to evaluate the contribution of Cx36 in the control of insulin secretion and content. These experiments have demonstrated that tight levels of Cx36 are crucial for proper function of insulin-producing cells. Moreover, stably transfected insulin-secreting MIN6 cells with a cx36 antisense cDNA impaired the synchronization of glucose-induced Ca( 2ϩ ) oscillations and insulin secretion in response to glucose (17). These data provided evidence that proper storage of insulin as well as the regulation of insulin release required that the levels of Cx36 be maintained within native values.The objective of the present study was to characterize the mechanisms of cell-specific expression of Cx36. The presence of several gene transcripts in pancreatic ␤-cells and neuronal cells was correlated with the absence in these cell types of a transcription factor named NRSF/REST (neuron-restrictive silencer factor/repressor element silencing transcription factor) (18). NRSF/REST binds to a 21-bp cis element named neuronal restrictive silencer element (NRSE). Through this NRSE, NRSF/REST has been identified as a negative regulatory system that silences neuronal gene expression in non-neuronal tissues, neuronal precursor cells, and certain differentiated

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“…Moreover, the human sequence contains a YY1-like binding site and a consensus mammary gland factor binding site (276). The region Ϫ140 to Ϫ113 of the Cx26 promoter includes an Sp binding site overlapping with an AP-2 binding site which are responsible for the upregulation of Cx26 in the myometrium during pregnancy and in the mammary gland during lactation (590).…”

Section: Transcriptional Regulation and Gene Promotersmentioning

confidence: 99%

Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

Sáez

Berthoud

Brañes

et al. 2003

Physiological Reviews

1,057

952

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Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.

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Involving AP‐2 transcription factor in connexin 26 up‐regulation during pregnancy and lactation

Cited by 8 publications

References 35 publications

Investigation of the Transcriptional Changes Underlying Functional Defects in the Mammary Glands of Prolactin Receptor Knockout Mice

Investigation of the Transcriptional Changes Underlying Functional Defects in the Mammary Glands of Prolactin Receptor Knockout Mice

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

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