The first cell fate decision in development occurs at the blastocyst stage with the emergence of the trophectoderm (TE) and the inner cell mass (ICM). The TE is the precursor population of all major placental cell types. Reflecting this developmental plasticity, trophoblast stem cells (TSCs) can be derived from the TE of mouse blastocysts. TSCs have proven an invaluable research tool to study processes of early placentation in vitro. Despite the placenta’s central role in reproduction, our understanding of the regulatory networks that orchestrate TSC self-renewal and differentiation remains incomplete. In this project, I characterised an epigenetic modifier, KDM1B, for its role in TSC self-renewal and differentiation. I identified this factor as a putative novel regulator of trophoblast stem cell fate and in vitro differentiation from transcriptomics data as its expression is markedly induced at the onset of differentiation. Furthermore, Kdm1b had been implicated in mouse development and placentation, via directing DNA methylation of maternal imprints in the oocyte. KDM1B is a histone lysine demethylase whose activity is directed to H3K4me1 and H3K4me2, particularly within the gene body of actively transcribed genes. By generating CRISPR-Cas9-mediated knockout TSCs ablated for Kdm1b, I show that Esrrb is consistently down-regulated but Gcm1 is up-regulated in Kdm1b-/- TSC clones as measured by RT-qPCR, indicative of precocious differentiation into the syncytiotrophoblast lineage. By performing a large cohort of integrated genome-wide analyses, notably RNA-seq and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) for the relevant histone modifications H3K4me1, H3K4me2, H3K4me3 and H3K36me3, I show that KDM1B regulates intragenic H3K4me1-marked enhancers, while not impacting H3K4me3. Remarkably, KDM1B null trophoblast cells also show an increased instability of chromosome 13, the same chromosome on which Kdm1b itself is located. This chromosome hosts several gene families that arose from gene duplication events, with vital roles in trophoblast development. The instability of chromosome 13 that gave rise to these gene families is apparently exacerbated by loss of KDM1B, or by CRISPR Cas9-induced cutting of the chromosome. In addition to interrogating the role of KDM1B during differentiation, I utilised the transcriptomic and ChIP-seq data to identify several trophoblast-specific transcripts via location of distal H3K4me3 peaks. Using previously published ChIP-seq data in combination with my own, I link enhancer activity in stem cells to gene expression throughout differentiation. Finally, I identify a striking and novel redistribution of H3K36me3 in 5 day differentiated trophoblast cells, to the promoter regions of expressed genes. In conclusion, this work presents an in-depth analysis of the transcriptional and epigenomic rearrangements that occur both in WT trophoblast and as a consequence of Kdm1b deletion. These data lend important insights into the functions of this epigenetic modifier in the fine-tuning of the transcriptional networks that direct TSC self-renewal and differentiation.