Anwyn Apedaile’s research while affiliated with QIMR Berghofer Medical Research Institute and other places

... The WIZ variant identified in patient S1 (sufficient bladder) and the CYP4F22 and TP63 variants identified in patient l1 and l5, respectively (insufficient bladders) are classified as variants of uncertain significance by Varsome (Kopanos et al., 2019). WIZ is perhaps the most interesting candidate to evaluate for causation because homozygosity for null alleles results in embryonic lethality in mouse models (Daxinger et al., 2013). ...

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Rare exonic CELSR3 variants identified in Bladder Exstrophy Epispadias Complex

... Beyond its role in cancer, EIF3H has garnered interest as a candidate gene associated with Microcephaly-Thin Corpus Callosum syndrome, highlighting its potential relevance to maxillofacial developmental processes 64 . Intriguingly, studies in mice have revealed that homozygous mutants for the eIF3h MommeD12 and eIF3h MommeD38 mutations experience embryonic lethality at E9.5, emphasizing its vital role during early embryonic development 65 . Moreover, in zebrafish embryogenesis, eif3h has been found to play a pivotal role in the development of various organs, including the brain, heart, vasculature, and lateral line 66 . ...

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Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis

... Xist RNA physically coats the prospective inactive X-chromosome in cis and triggers a series of events (Penny et al. 1996;Engreitz et al. 2013;Gayen et al. 2016) by recruiting chromatin remodelers, transcriptional repressors and other RNA-binding proteins that ultimately lead to chromosomewide transcriptional silencing and reconfigures X-chromosome architecture into condensed heterochromatin (Zhao et al. 2008;Chu et al. 2015;Minajigi et al. 2015;Cerase et al. 2015;Bonora and Disteche 2017;Wang et al. 2018;Loda and Heard 2019;Colognori et al. 2020;Boeren and Gribnau 2021;Markaki et al. 2021). This condensation is accomplished through the depletion of active histone marks such as H3K4me3, H3K27ac, H3K9ac and H3K36me3 (Jeppesen and Turner 1993;Chaumeil et al. 2002;Janiszewski et al. 2019;Brockdorff et al. 2020;Dixon-McDougall and Brown 2022) and deposition of the repressive histone marks such as H2AK119Ub, H3K27me3, H3K9me2/3, H4k20me3 (Plath et al. 2003;Kohlmaier et al. 2004;Brockdorff 2017;Żylicz et al. 2019) as well as incorporation of macroH2A (Costanzi and Pehrson 1998;Chadwick and Willard 2002;Changolkar and Pehrson 2006) and DNA methylation (Norris et al. 1991;Gendrel et al. 2012;Pasque et al. 2014;Yagi et al. 2020). ...

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Multifaceted role of CTCF in X-chromosome inactivation

... An intriguing possibility relates to the histone PTM H3K9me3 which is enhanced/redistributed on Xi following recruitment of the chromosomal protein SmcHD1 (Ichihara, Nagao, Sakaguchi, Obuse, & Sado, 2022). SmcHD1 in turn is required for CpG methylation at the majority (~90%) of Xi CGIs (Blewitt et al., 2008;Gendrel et al., 2012). Potential mechanisms include direct binding of DNMT3B to H3K9me3, and here it is interesting to note that the protein ATRX has an ADD domain which has been shown to mediate H3K9me3 binding (Iwase et al., 2011). ...

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PWWP-ADD and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation

... These sites, and the long genes found within them, are often hotspots for the chromosomal rearrangements and deletions that arise in cancers and other genetic diseases (Smith et al., 2006). Replication, transcription, and chromatin organisation are also intricately inter-connected, with each influencing the other (Ehrenhofer-Murray, 2004;Sequeira-Mendes et al., 2009;Turner and Woodworth, 2001;Tabancay Jr and Forsburg, 2006;Kadonaga, 1998). In particular, chromatin remodelling regulates the accessibility of regulatory factors, influencing both gene expression and the replication process. ...

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DNA replication timing reveals genome-wide features of transcription and fragility

... Female ESCs often lose one X chromosome in culture 38 . Homozygous X 5c-∆ X 5c-∆ ESCs lost an X chromosome more rapidly compared to both the WT and heterozygous X 5c-fl X 5c-∆ female ESCs ( Figure S6). ...

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Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene Pair Kdm5c-Kdm5d

... Thus, vacating CTCF from the inactivating X except at specific escape loci is believed to contribute to an overall loss of TADs and compartments (Giorgetti et al. 2016). Along with Xist a noncanonical SMC protein SMCHD1 (structural-maintenance-of-chromosomes hinge domain containing 1) enriched on inactive X (Blewitt et al. 2008), suppresses CTCF binding on inactive X and weakens TADs and brings decompartmentalization thereby contributes for X chromosome architectural transformation (Wang et al. 2018). ...

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Multifaceted role of CTCF in X-chromosome inactivation