PDBsum entry 6t90

Transcription

PDB id: 6t90

Contents

Protein chains

94 a.a.

82 a.a.

109 a.a.

93 a.a.

73 a.a.

74 a.a.

DNA/RNA

Ligands

PTD ×9

PDB id:

6t90

Name:

Transcription

Title:

Oct4-sox2-bound nucleosome - shl-6

Structure:

Histone h3.1. Chain: a. Synonym: histone h3/a,histone h3/b,histone h3/c,histone h3/d,histone h3/f,histone h3/h,histone h3/i,histone h3/j,histone h3/k,histone h3/l. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hist1h3a, h3fa, hist1h3b, h3fl, hist1h3c, h3fc, hist1h3d, h3fb, hist1h3e, h3fd, hist1h3f, h3fi, hist1h3g, h3fh, hist1h3h, h3fk, hist1h3i, h3ff, hist1h3j, h3fj. Expressed in: escherichia coli 'bl21-gold(de3)plyss ag'. Expression_system_taxid: 866768. Gene: hist1h4a, h4/a, h4fa, hist1h4b, h4/i, h4fi, hist1h4c, h4/g,

Authors:

A.K.Michael,G.Kempf,S.Cavadini,R.D.Bunker,N.H.Thoma

Key ref:

A.K.Michael et al. (2020). Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science, 368, 1460-1465. PubMed id: 32327602 DOI: 10.1126/science.abb0074

Date:

25-Oct-19 Release date: 06-May-20

Protein chains

P68431  (H31_HUMAN) -  Histone H3.1 from Homo sapiens

Seq: 136 a.a.

Struc: 94 a.a.

Protein chains

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 82 a.a.

Protein chains

P04908  (H2A1B_HUMAN) -  Histone H2A type 1-B/E from Homo sapiens

Seq: 130 a.a.

Struc: 109 a.a.

Protein chains

P06899  (H2B1J_HUMAN) -  Histone H2B type 1-J from Homo sapiens

Seq: 126 a.a.

Struc: 93 a.a.

Protein chain

P42212  (GFP_AEQVI) -  Green fluorescent protein from Aequorea victoria

Seq: 238 a.a.

Struc: 73 a.a.*

Protein chain

Q01860  (PO5F1_HUMAN) -  POU domain, class 5, transcription factor 1 from Homo sapiens

Seq: 360 a.a.

Struc: 73 a.a.

Protein chain

P48431  (SOX2_HUMAN) -  Transcription factor SOX-2 from Homo sapiens

Seq: 317 a.a.

Struc: 74 a.a.

* PDB and UniProt seqs differ at 53 residue positions (black crosses)

DNA/RNA chains

G-G-A-G-A-C-T-T-T-G-T-T-A-T-G-C-A-A-A-T-C-C-G-C-T-C-A-A-T-T-G-G-T-C-G-T-A-G-A- 141 bases

G-A-T-G-T-A-T-A-T-A-T-C-T-G-A-C-A-C-G-T-G-C-C-T-G-G-A-G-A-C-T-A-G-G-G-A-G-T-A- 141 bases

DOI no: 10.1126/science.abb0074

Science 368:1460-1465 (2020)

PubMed id: 32327602

Mechanisms of OCT4-SOX2 motif readout on nucleosomes.

A.K.Michael, R.S.Grand, L.Isbel, S.Cavadini, Z.Kozicka, G.Kempf, R.D.Bunker, A.D.Schenk, A.Graff-Meyer, G.R.Pathare, J.Weiss, S.Matsumoto, L.Burger, D.Schübeler, N.H.Thomä.

ABSTRACT

Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo-electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.