Search

Your search keyword '"Holland, Michelle L."' showing total 29 results
Start Over Author "Holland, Michelle L."
29 results on '"Holland, Michelle L."'

8. Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states

Author

Rodriguez‑Algarra, Francisco, Seaborne, Robert A. E., Danson, Amy F., Yildizoglu, Selin, Yoshikawa, Harunori, Law, Pui Pik, Ahmad, Zakaryya, Maudsley, Victoria A., Brew, Ama, Holmes, Nadine, Ochôa, Mateus, Hodgkinson, Alan, Marzi, Sarah J., Pradeepa, Madapura M., Loose, Matthew, Holland, Michelle L., Rakyan, Vardhman K., Rodriguez‑Algarra, Francisco, Seaborne, Robert A. E., Danson, Amy F., Yildizoglu, Selin, Yoshikawa, Harunori, Law, Pui Pik, Ahmad, Zakaryya, Maudsley, Victoria A., Brew, Ama, Holmes, Nadine, Ochôa, Mateus, Hodgkinson, Alan, Marzi, Sarah J., Pradeepa, Madapura M., Loose, Matthew, Holland, Michelle L., and Rakyan, Vardhman K.

Abstract

Background: Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this variation impacts epigenetic states and expression of the rDNA has thus far not been performed. Results: Using a combination of long- and short-read sequencing, we establish that 45S rDNA units in the C57BL/6J mouse strain exist as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. DNA methylation dynamics at these haplotypes are dichotomous and life-stage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during aging only. On the other hand, individual rDNA units in human show limited evidence of genetic haplotypes, and hence little discernible correlation between genetic and epigenetic states. However, in both species, adjacent units show similar epigenetic profiles, and the overall epigenetic state at rDNA is strongly positively correlated with the total rDNA copy number. Analysis of different mouse inbred strains reveals that in some strains, such as 129S1/SvImJ, the rDNA copy number is only approximately 150 copies per diploid genome and DNA methylation levels are < 5%. Conclusions: Our work demonstrates that rDNA-associated genetic variation has a considerable influence on rDNA epigenetic state and consequently rRNA expression outcomes. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases.

Published
2022

9. Additional file 1 of Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states

Author

Rodriguez-Algarra, Francisco, Seaborne, Robert A. E., Danson, Amy F., Yildizoglu, Selin, Yoshikawa, Harunori, Law, Pui Pik, Ahmad, Zakaryya, Maudsley, Victoria A., Brew, Ama, Holmes, Nadine, Och��a, Mateus, Hodgkinson, Alan, Marzi, Sarah J., Pradeepa, Madapura M., Loose, Matthew, Holland, Michelle L., and Rakyan, Vardhman K.

Subjects
Data_FILES
Abstract

Additional file 1. Extended data analysis methods.

Published
2022
Full Text
View/download PDF

10. Additional file 3 of Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states

Author

Rodriguez-Algarra, Francisco, Seaborne, Robert A. E., Danson, Amy F., Yildizoglu, Selin, Yoshikawa, Harunori, Law, Pui Pik, Ahmad, Zakaryya, Maudsley, Victoria A., Brew, Ama, Holmes, Nadine, Och��a, Mateus, Hodgkinson, Alan, Marzi, Sarah J., Pradeepa, Madapura M., Loose, Matthew, Holland, Michelle L., and Rakyan, Vardhman K.

Abstract

Additional file 3. Supplementary figures S1-S20.

Published
2022
Full Text
View/download PDF

12. Identification of MAZ as a novel transcription factor regulating erythropoiesis

Author

Deen, Darya, Butter , Falk, Holland, Michelle L., Samara, Vasiliki, Sloane-Stanley, Jacqueline A., Ayyub, Helena, Mann, Matthias, Garrick, David, and Vernimmen, Douglas

Subjects
hemic and lymphatic diseases
Abstract

Erythropoiesis requires a combination of ubiquitous and tissue-specific transcription factors. Here, through DNA affinity purification followed by mass spectrometry, we have identified the widely expressed protein MAZ (Myc-associated zinc finger) as a transcription factor that binds to the promoter of the erythroid-specific human α-globin gene. Genome-wide mapping in primary human erythroid cells revealed that MAZ also occupies active promoters as well as GATA1-bound enhancer elements of key erythroid genes. Consistent with an important role during erythropoiesis, knockdown of MAZ in primary human erythroid cells impairs erythroid differentiation, and genetic variants in the MAZ locus are associated with clinically important human erythroid traits. Taken together, these findings reveal the Zinc-finger transcription factor MAZ to be a previously unrecognised regulator of the erythroid differentiation program.

Published
2020
Full Text
View/download PDF

13. Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states

Author

Rodriguez-Algarra, Francisco, primary, Seaborne, Robert A E, additional, Danson, Amy F, additional, Yildizoglu, Selin, additional, Yoshikawa, Harunori, additional, Law, Pui Pik, additional, Ahmad, Zakaryya, additional, Maudsley, Victoria A, additional, Brew, Ama, additional, Holmes, Nadine, additional, Ochôa, Mateus, additional, Hodgkinson, Alan, additional, Marzi, Sarah J, additional, Pradeepa, Madapura M, additional, Loose, Matthew, additional, Holland, Michelle L, additional, and Rakyan, Vardhman K, additional

Published
2021
Full Text
View/download PDF

26. Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans

Author

Beyan, Huriya, primary, Down, Thomas A., additional, Ramagopalan, Sreeram V., additional, Uvebrant, Kristina, additional, Nilsson, Anita, additional, Holland, Michelle L., additional, Gemma, Carolina, additional, Giovannoni, Gavin, additional, Boehm, Bernhard O., additional, Ebers, George C., additional, Lernmark, Åke, additional, Cilio, Corrado M., additional, Leslie, R. David, additional, and Rakyan, Vardhman K., additional

Published
2012
Full Text
View/download PDF

28. CB2and TRPV1 receptors mediate cannabinoid actions on MDR1expression in multidrug resistant cells

Author

Arnold, Jonathon C., Hone, Phoebe, Holland, Michelle L., and Allen, John D.

Abstract

Background: Cannabis is the most widely used illicit drug in the world that is often used by cancer patients in combination with conventional anticancer drugs. Multidrug resistance (MDR) is a major obstacle in the treatment of cancer. An extensively characterized mechanism of MDR involves overexpression of P-glycoprotein (P-gp), which reduces the cellular accumulation of cytotoxic drugs in tumor cells. Methods: Here we examined the role of cannabinoid receptors and transient receptor potential vanilloid type 1 (TRPV1) receptors in the effects of plant-derived cannabinoids on MDR1mRNA expression in MDR CEM/VLB100cells which overexpress P-gp due to MDR1gene amplification. Results: We showed that both cannabidiol (CBD) and ?9-tetrahydrocannabinol (?9-THC) (10 µM) transiently induced the MDR1transcript in P-gp overexpressing cells at 4 but not 8 or 48 h incubation durations. CBD and THC also concomitantly increased P-gp activity as measured by reduced accumulation of the P-gp substrate Rhodamine 123 in these cells with a maximal inhibitory effect observed at 4 h that slowly diminished by 48 h. CEM/VLB100cell lines were shown to express CB2 and TRPV1 receptors. ?9-THC effects on MDR1expression were mediated by CB2 receptors. The effects of CBD were not mediated by either CB2 or TRPV1 receptors alone, however, required activation of both these receptors to modulate MDR1mRNA expression. Conclusion: This is the first evidence that CB2and TRPV1receptors cooperate to modulate MDR1expression.

Published
2012
Full Text
View/download PDF

29. Deciphering the Role of the Non-Coding Genome in Regulating Gene-Diet Interactions.

Author

Law, Pui-Pik and Holland, Michelle L.

Abstract

Protein encoding genes constitute a small fraction of mammalian genomes. In addition to the protein coding genes, there are other functional units within the genome that are transcribed, but not translated into protein, the so called non-coding RNAs. There are many types of non-coding RNAs that have been identified and shown to have important roles in regulating gene expression either at the transcriptional or post-transcriptional level. A number of recent studies have highlighted that dietary manipulation in mammals can influence the expression or function of a number of classes of non-coding RNAs that contribute to the protein translation machinery. The identification of protein translation as a common target for nutritional regulation underscores the need to investigate how this may mechanistically contribute to phenotypes and diseases that are modified by nutritional intervention. Finally, we describe the state of the art and the application of emerging '-omics' technologies to address the regulation of protein translation in response to diet. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results