Compositions and methods for epigenome editing
Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.
1. A fusion protein comprising two heterologous polypeptide domains, wherein the first polypeptide domain comprises a Clustered Regularly Interspaced Short Palindromic Repeats associated (Cas) protein, wherein the second polypeptide domain comprises a p300 histone acetyltransferase effector domain, wherein the fusion protein activates transcription of a target gene by activating distal regulatory elements, and wherein the fusion protein comprises the polypeptide sequence of SEQ ID NO: 140, SEQ ID NO: 141, or SEQ ID NO: 149.
2. A kit comprising the fusion protein of claim 1 .
3. A fusion protein comprising two heterologous polypeptide domains,
wherein the first polypeptide domain comprises a Clustered Regularly Interspaced Short Palindromic Repeats associated (Cas) protein,
wherein the second polypeptide domain comprises a p300 histone acetyltransferase effector domain,
wherein the fusion protein activates transcription of a target gene by activating distal regulatory elements, and
wherein the first polypeptide domain comprises the polypeptide sequence of SEQ ID NO: 10 and the second polypeptide domain comprises the polypeptide sequence of SEQ ID NO: 3, or the first polypeptide domain comprises the polypeptide sequence of SEQ ID NO: 1 and the second polypeptide domain comprises the polypeptide sequence of SEQ ID NO: 2.
4. A kit comprising the fusion protein of claim 3 .