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The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis.

Parsons MJ, Brancaccio M, Sethi S, Maywood ES, Satija R, Edwards JK, Jagannath A, Couch Y, Finelli MJ, Smyllie NJ, Esapa C, Butler R, Barnard AR, Chesham JE, Saito S, Joynson G, Wells S, Foster RG, Oliver PL, Simon MM, Mallon AM, Hastings MH, Nolan PM - Cell (2015)

Bottom Line: Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3(Sci/+) SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed.Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3(Sci/+) SCN slices.In conclusion, by cloning Zfhx3(Sci), we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms.

View Article: PubMed Central - PubMed

Affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.

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Conservation of ZFHX3 Binding Sites across Species, Related to Experimental ProceduresA multiple sequence alignment for ZFHX3 binding sites for Afp, Mrf4, Pit1, and Muc5ac reveals conservation of the motif across both primates and placental mammals.
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figs6: Conservation of ZFHX3 Binding Sites across Species, Related to Experimental ProceduresA multiple sequence alignment for ZFHX3 binding sites for Afp, Mrf4, Pit1, and Muc5ac reveals conservation of the motif across both primates and placental mammals.

Mentions: To construct a motif-binding model for ZFHX3, we searched the literature for previously identified binding sites (Figure S6). We used sequences from genes that are directly regulated through a characterized binding motif and generated the consensus sequence using a mixture model by multiple EM (expectation maximization) for motif elicitation (MEME) (Bailey and Elkan, 1994).


The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis.

Parsons MJ, Brancaccio M, Sethi S, Maywood ES, Satija R, Edwards JK, Jagannath A, Couch Y, Finelli MJ, Smyllie NJ, Esapa C, Butler R, Barnard AR, Chesham JE, Saito S, Joynson G, Wells S, Foster RG, Oliver PL, Simon MM, Mallon AM, Hastings MH, Nolan PM - Cell (2015)

Conservation of ZFHX3 Binding Sites across Species, Related to Experimental ProceduresA multiple sequence alignment for ZFHX3 binding sites for Afp, Mrf4, Pit1, and Muc5ac reveals conservation of the motif across both primates and placental mammals.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4537516&req=5

figs6: Conservation of ZFHX3 Binding Sites across Species, Related to Experimental ProceduresA multiple sequence alignment for ZFHX3 binding sites for Afp, Mrf4, Pit1, and Muc5ac reveals conservation of the motif across both primates and placental mammals.
Mentions: To construct a motif-binding model for ZFHX3, we searched the literature for previously identified binding sites (Figure S6). We used sequences from genes that are directly regulated through a characterized binding motif and generated the consensus sequence using a mixture model by multiple EM (expectation maximization) for motif elicitation (MEME) (Bailey and Elkan, 1994).

Bottom Line: Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3(Sci/+) SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed.Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3(Sci/+) SCN slices.In conclusion, by cloning Zfhx3(Sci), we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms.

View Article: PubMed Central - PubMed

Affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.

Show MeSH