Project Details
Projekt
Understanding the functional role of HMG20A and its associated complexes in regulating developmental transcription programs
Subject Area
General Genetics and Functional Genome Biology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 523755719
Histone variants are important inducers of targeted chromatin structure changes within eukaryotes, thereby controlling vital DNA-based processes. The evolutionary conserved H2A.Z variant is, among other processes, essential for the regulation of transcription and thus influences stem cell differentiation and embryo development. One possibility of how H2A.Z can regulate these processes is through the recruitment of different chromatin-modifying proteins to H2A.Z-marked regulatory genomic regions, such as promoters and enhancers. We were able to identify, among others, PWWP2A and HMG20A as novel H2A.Z interactors in diverse published and unpublished quantitative mass-spectrometry screens. We could show that both proteins associate with each other and are important for proper craniofacial development in Xenopus, most likely due to the regulation of genes that control migration and differentiation of neural crest cells. Interestingly, HMG20A interacts also with non-H2A.Z-associated complexes and regulates, in addition, heart development in Xenopus and cardiomyocyte differentiation of mouse embryonic stem cells. We now plan to investigate in a cooperative project, i) which specific processes during craniofacial and heart development are controlled by HMG20A, ii) which of the different HMG20A-associated complexes are required for the transcription of genes that are needed for proper neural crest and heart development and iii) whether HMG20A controls the expression of dnmt3l and thereby influences DNA methylation pattern. For these purposes, we will combine experimental developmental in vivo (Xenopus) with mechanistic in vitro (mouse embryonic stem cell) approaches to obtain a better understanding of HMG20As’ function(s) during differentiation processes. We will, among others, execute depletion and rescue experiments, genome-wide CUT&RUN and RNA-seq analyses as well as high-resolution microscopy techniques. In summary, we will collectively apply state-of-the-art experiments to better understand the functional relevance of HMG20A in H2A.Z-dependent and -independent transcription processes during early embryo development.
DFG Programme
Research Grants
