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A role for Id2 in regulating photic entrainment of the mammalian circadian system.

Duffield GE, Watson NP, Mantani A, Peirson SN, Robles-Murguia M, Loros JJ, Israel MA, Dunlap JC - Curr. Biol. (2009)

Bottom Line: Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus.In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK.These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA. duffield.2@nd.edu

ABSTRACT
Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2(-/-) mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4(-/-) mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

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Id Genes Are Rhythmically Expressed in the SCN and Heart(A–F) The following are shown: A, Id1; B, Id2; C, Id3; D, Id4 (only expressed in SCN); E, Bmal1; and F, mPer2. SCN profiles are left and heart profiles are right. Mouse tissue was collected under constant dark conditions (3 days after transition from 12:12 LD cycle to DD). SCN samples were collected as pooled frozen tissue punches (n = 6 mice per time point). Heart samples were analyzed for each animal (n = 3–6 mice per time point). Quantitative gene expression was measured by real-time quantitative RT-PCR (SYBR green, ABI 7700, normalized to 18S and acidic ribosomal phosphoprotein, ARP). Values are n-fold-change relative to nadir of expression and mean ± SEM for heart. The peak phase of rhythm is indicated by the gray bar. Subjective day and night are highlighted by white and gray panels below (F), respectively. Statistical analysis of heart samples reveals significant rhythms (one-factor ANOVA, followed by Dunnett's post-hoc t tests, ∗p < 0.05).
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fig1: Id Genes Are Rhythmically Expressed in the SCN and Heart(A–F) The following are shown: A, Id1; B, Id2; C, Id3; D, Id4 (only expressed in SCN); E, Bmal1; and F, mPer2. SCN profiles are left and heart profiles are right. Mouse tissue was collected under constant dark conditions (3 days after transition from 12:12 LD cycle to DD). SCN samples were collected as pooled frozen tissue punches (n = 6 mice per time point). Heart samples were analyzed for each animal (n = 3–6 mice per time point). Quantitative gene expression was measured by real-time quantitative RT-PCR (SYBR green, ABI 7700, normalized to 18S and acidic ribosomal phosphoprotein, ARP). Values are n-fold-change relative to nadir of expression and mean ± SEM for heart. The peak phase of rhythm is indicated by the gray bar. Subjective day and night are highlighted by white and gray panels below (F), respectively. Statistical analysis of heart samples reveals significant rhythms (one-factor ANOVA, followed by Dunnett's post-hoc t tests, ∗p < 0.05).

Mentions: Circadian regulation of Id genes was determined in SCN and heart tissue collected from mice held in constant darkness (DD) (Figure 1). In the SCN, expression of all four Id genes was rhythmic, with peak phases occurring near the middle of subjective night at circadian time (CT) 16 to CT20. In the heart, peak phases of Id1, Id2, and Id3 span the middle to late subjective day, CT8 to CT12, whereas expression of Id4 was below the level of detection. Impressively, Id gene expression showed a distinct circadian pattern in all tissues examined, namely SCN, heart, liver (peak phase at CT4; T. Hou and G.E.D., data not shown), and fibroblasts.


A role for Id2 in regulating photic entrainment of the mammalian circadian system.

Duffield GE, Watson NP, Mantani A, Peirson SN, Robles-Murguia M, Loros JJ, Israel MA, Dunlap JC - Curr. Biol. (2009)

Id Genes Are Rhythmically Expressed in the SCN and Heart(A–F) The following are shown: A, Id1; B, Id2; C, Id3; D, Id4 (only expressed in SCN); E, Bmal1; and F, mPer2. SCN profiles are left and heart profiles are right. Mouse tissue was collected under constant dark conditions (3 days after transition from 12:12 LD cycle to DD). SCN samples were collected as pooled frozen tissue punches (n = 6 mice per time point). Heart samples were analyzed for each animal (n = 3–6 mice per time point). Quantitative gene expression was measured by real-time quantitative RT-PCR (SYBR green, ABI 7700, normalized to 18S and acidic ribosomal phosphoprotein, ARP). Values are n-fold-change relative to nadir of expression and mean ± SEM for heart. The peak phase of rhythm is indicated by the gray bar. Subjective day and night are highlighted by white and gray panels below (F), respectively. Statistical analysis of heart samples reveals significant rhythms (one-factor ANOVA, followed by Dunnett's post-hoc t tests, ∗p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2648875&req=5

fig1: Id Genes Are Rhythmically Expressed in the SCN and Heart(A–F) The following are shown: A, Id1; B, Id2; C, Id3; D, Id4 (only expressed in SCN); E, Bmal1; and F, mPer2. SCN profiles are left and heart profiles are right. Mouse tissue was collected under constant dark conditions (3 days after transition from 12:12 LD cycle to DD). SCN samples were collected as pooled frozen tissue punches (n = 6 mice per time point). Heart samples were analyzed for each animal (n = 3–6 mice per time point). Quantitative gene expression was measured by real-time quantitative RT-PCR (SYBR green, ABI 7700, normalized to 18S and acidic ribosomal phosphoprotein, ARP). Values are n-fold-change relative to nadir of expression and mean ± SEM for heart. The peak phase of rhythm is indicated by the gray bar. Subjective day and night are highlighted by white and gray panels below (F), respectively. Statistical analysis of heart samples reveals significant rhythms (one-factor ANOVA, followed by Dunnett's post-hoc t tests, ∗p < 0.05).
Mentions: Circadian regulation of Id genes was determined in SCN and heart tissue collected from mice held in constant darkness (DD) (Figure 1). In the SCN, expression of all four Id genes was rhythmic, with peak phases occurring near the middle of subjective night at circadian time (CT) 16 to CT20. In the heart, peak phases of Id1, Id2, and Id3 span the middle to late subjective day, CT8 to CT12, whereas expression of Id4 was below the level of detection. Impressively, Id gene expression showed a distinct circadian pattern in all tissues examined, namely SCN, heart, liver (peak phase at CT4; T. Hou and G.E.D., data not shown), and fibroblasts.

Bottom Line: Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus.In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK.These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA. duffield.2@nd.edu

ABSTRACT
Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2(-/-) mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4(-/-) mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

Show MeSH
Related in: MedlinePlus