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BPTF is essential for murine neocortical development

ABSTRACT: BPTF is essential for murine neocortical development

PROVIDER: PRJNA647223 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12265415_1.fastq.gz	Fastqsanger.gz
	SRR12265415_2.fastq.gz	Fastqsanger.gz
	SRR12265416_1.fastq.gz	Fastqsanger.gz
	SRR12265416_2.fastq.gz	Fastqsanger.gz
	SRR12265417_1.fastq.gz	Fastqsanger.gz

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BPTF is essential for murine neocortical development

Project description:Chromatin remodeling complexes modulate DNA accessibility permitting neuronal progenitor cells to proliferate and differentiate to form the mammalian neocortex. In the case of BPTF, the major subunit of a chromatin remodelling complex called NURF, mutations leading to its haploinsufficiency have been linked to cause a recently annotated human neurodevelopmental disorder called NEDDFL (Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies). Patients with this syndrome are mainly characterized with microcephaly and intellectual disability. We conditionally knockout (cKO) the Bptf gene during neocortical neurogenesis to analyze its role during embryonic and postnatal brain development. The Bptf cKO animals reveal significant forebrain hypoplasia. During cortical neurogenesis, the cKOs show a reduction in intermediate neuronal progenitor (INP) cells, an increase in apoptosis as well as a prolonged cell cycle of proliferating progenitors. Similarly, the cKOs have decreased proportions of pyramidal neurons expressing Ctip2 and Foxp1. Lastly, our RNA-seq analysis delineates gene pathways deregulated by Bptf’s removal, which are involved in neurogenesis and neuronal differentiation. Our results indicate that Bptf is critical for murine telencephalon neurogenesis. The hypoplasia demonstrated in the mouse model can resemble the microcephaly displayed by the human NEDFFL patients, highlighting the relevance of chromatin remodelling complexes during intricate neural developmental processes.

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The chromatin remodeler Bptf activates a stemness gene-expression program essential for the maintenance of adult hematopoietic stem cells [ChIP-Seq]

Project description:Bptf, a component of NURF chromatin-remodeling complex, is essential for maintaining the pool size and function of hematopoietic stem cells (HSCs). Genome-wide transcriptome profiling revealed that Bptf loss caused down-regulation of HSC-specific gene-expression programs, which included master transcription factors (such as Meis1, Pbx1, and Lmo2) known to be required for HSC maintenance and self-renewal. Bptf directly bound to the promoter of ‘stemness’ TF genes, potentiating their transcription and DNA accessibility.

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The chromatin remodeler Bptf activates a stemness gene-expression program essential for the maintenance of adult hematopoietic stem cells [ATAC-Seq]

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