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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq II]

ABSTRACT: HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq II]

PROVIDER: PRJNA793916 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17417788_1.fastq.gz	Fastqsanger.gz
	SRR17417788_2.fastq.gz	Fastqsanger.gz
	SRR17417789_1.fastq.gz	Fastqsanger.gz
	SRR17417789_2.fastq.gz	Fastqsanger.gz
	SRR17417790_1.fastq.gz	Fastqsanger.gz

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer 1 transcription repression and leukemia cell differentiation block

Project description:Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we made use of mass spectrometry approaches. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is colocated on chromatin genome-wide with GFI1 and LSD1; the strongest HMG20B binding colocates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukaemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing the interaction on chromatin of LSD1 with GFI1. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukaemia cell differentiation block.

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [RNA-seq]

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq II]

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq I]

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block

Project description:HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [RNA-seq]

Project description:HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [RNA-seq]

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq I]

Project description:HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [ChIP-seq I]

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HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block

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microRNA expression in bone marrow cells from Gfi1 deficient mice

Project description:Growth factor independent-1 (Gfi1) is a zinc finger transcription factor with a SNAG amino-terminal repressor domain and is critically required for normal myelopoesis. Gfi1 is normally expressed in HSCs and induced during differentiation from CMPs to GMPs. Gfi1 loss-of-function mutation in mice and humans induces an arrest during myeloid differentiation and an absolute block to the formation mature neutrophils. This comparative microarray study was initiated to identify microRNAs which are potentially regulated by Gfi1 during granulopoiesis. The Gfi1 null allele from Orkin (deletion of exons 2 and 3) was backcrossed to B6 or Balb/c mice for at least 7 generations. RNA was isolated from low density bone marrow samples from Gfi1+/+ and Gfi1-/- B6 littermates, as well as Gfi1+/+ and Gfi1-/- Balb/c littermates.

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microRNA expression in bone marrow cells from Gfi1 deficient mice

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