Targeted histone acetylation

• US 10,570,378 B2
• Filed: 02/28/2013
• Issued: 02/25/2020
• Est. Priority Date: 02/28/2012
• Status: Active Grant

• Current Assignee: Sigma-Aldrich Co. LLC (Merck & Co., Inc.)
• Original Assignee: Sigma-Aldrich Co. LLC (Merck & Co., Inc.)
• Inventors: Ji, Qingzhou, Kreader, Carol
• Primary Examiner(s): Tsay, Marsha
• Application Number:
  US14/381,381
• Publication Number:
  US 20150079657A1
• Time in Patent Office: 2,553 Days
• Field of Search: None
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 2319/09 containing a nuclear localisation signal
• CPC Class Codes: C07K 2319/80 containing a DNA binding domain, e.g. Lacl or Tet-repressor
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C07K 2319/915 containing a motif for acylation
• CPC Class Codes: C12N 9/1029 transferring groups other than amino-acyl groups (2.3.1)
• CPC Class Codes: C12Y 203/01048 Histone acetyltransferase (2.3.1.48)

Abstract

The present disclosure provides compositions and methods for acetylating histones at targeted chromosomal locations in a cell. In particular, the disclosure provides a fusion protein comprising a DNA binding domain and at least one histone acetyltransferase (HAT) domain, such that the DNA binding domain targets the fusion protein to a targeted chromosomal location and the HAT domain acetylates histones at the targeted location.

Claims

1. A fusion protein comprising a DNA binding domain and a domain having histone acetyltransferase activity that consists essentially of amino acids 1100-1750 of SEQ ID NO:

13 or amino acids 1284-1673 of SEQ ID NO;

13, wherein the DNA binding domain is a zinc finger DNA binding domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO;

2, SEQ ID NO;

9 and SEQ ID NO;

10.

2. The fusion protein of claim 1, wherein the DNA binding domain further comprises at least one nuclear localization signal, at least one cell-penetrating domain, at least one marker domain, or a combination thereof.

3. An isolated nucleic acid encoding the fusion protein of claim 1.

4. The isolated nucleic acid of claim 3, further comprising at least one expression control sequence.