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Genome-wide maps of histone modification and chromatin remodeler binding in acute myeloid leukemia blast cells and normal hematopoietic cells

ABSTRACT: We have used chromatin immunoprecipitation followed by high throughput sequencing to map regions of chromatin remodeler binding accompanied by histone modification state. We have used this data to distinguish between the transcriptional state of regulatory genes in leukemic and normal hematopoietic cells, and thus understand contribution of the chromatin remodeler towards leukemogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108976 | GEO | 2018/01/10

SECONDARY ACCESSION(S): PRJNA429274

REPOSITORIES: GEO

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Genome-wide maps of chromatin remodeler binding in acute myeloid leukemia cell line.

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Nucleosome recognition and DNA distortion by the Chd1 remodeler revealed at 2.6 Å resolution

Project description:Chromatin remodelers are ATP-dependent enzymes that reorganize nucleosomes within all eukaryotic genomes. The Chd1 remodeler specializes in shifting nucleosomes into evenly spaced arrays, a defining characteristic of chromatin in gene bodies that blocks spurious transcription initiation. Linked to some forms of autism and commonly mutated in prostate cancer, Chd1 is essential for maintaining pluripotency in stem cells. Here we report a complex of yeast Chd1 bound to a nucleosome in a nucleotide-free state, determined by cryo-electron microscopy (cryo-EM) to 2.6 Å resolution. The structure shows a bulge of the DNA tracking strand where the ATPase motor engages the nucleosome, consistent with an initial stage in DNA translocation. Unlike other remodeler-nucleosome complexes, nucleosomal DNA compensates for the remodeler-induced bulge with a bulge of the complementary DNA strand one helical turn downstream from the ATPase motor. Unexpectedly, the structure also reveals an N-terminal binding motif, called ChEx, which binds on the exit-side acidic patch of the nucleosome. The ChEx motif can displace a LANA-based peptide from the acidic patch, which suggests a means by which Chd1 remodelers may block competing chromatin remodelers from acting on the opposite side of the nucleosome.

2022-02-23 | PXD025287 | Pride

Genome-wide maps of histone modification and chromatin remodeler binding in acute myeloid leukemia blast cells and normal hematopoietic cells

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