User:Brian Boyle/Sandbox 1: Difference between revisions
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The MOZ Histone Acetyltransferase Complex is a tetramer consisting of MEAF6, ING5, BRPF1 and MOZ or MORF<ref name="Klein" />. Within BRPF1, there are two non-chromatin-binding modules surrounding the PZP domain that are responsible for its association with the MOZ HAT Complex. On the N-terminal side of the PZP, lies the MOZ/MORF binding domain<ref name="Lalonde">PMID:24065767</ref>. On the other side of the PZP domain, there is a small module involved in binding to ING5 and MEAF6<ref name="Ullah">PMID:18794358</ref>. BRPF1 seems to be required for the formation of the MOZ HAT complex, as it acts as a bridge associating MOZ or MORF with ING5 and MEAF6<ref name ="Ullah" />. | The MOZ Histone Acetyltransferase Complex is a tetramer consisting of MEAF6, ING5, BRPF1 and MOZ or MORF<ref name="Klein" />. Within BRPF1, there are two non-chromatin-binding modules surrounding the PZP domain that are responsible for its association with the MOZ HAT Complex. On the N-terminal side of the PZP, lies the MOZ/MORF binding domain<ref name="Lalonde">PMID:24065767</ref>. On the other side of the PZP domain, there is a small module involved in binding to ING5 and MEAF6<ref name="Ullah">PMID:18794358</ref>. BRPF1 seems to be required for the formation of the MOZ HAT complex, as it acts as a bridge associating MOZ or MORF with ING5 and MEAF6<ref name ="Ullah" />. | ||
== ''' | == '''Sequential and Structural Conservation in BRPF1''' == | ||
[[Image:Family IV bromodomain sequence alignment.JPG | thumb | 400x400px | Sequence alignment of family IV bromodomains by Clustal Omega.]] | |||
Bromodomains are categorized into several families based on sequence and structural similarity. The BRPF1 bromodomain belongs to family IV of bromodomains<ref name="Lloyd">PMID:28500727</ref>. Out of these bromodomain proteins, the BRPF3 bromodomain has the highest sequence identity with that of BRPF1 (66.2%). A specific asparagine residue is conserved across all bromodomains due to its integral role in acetyllysine recognition. | |||
PWWP domains have very low sequence and structural conservation. In fact, BRPF1 actually contains a PSYP motif rather than the canonical PWWP motif, however this change doesn't impact its ability to recognize methylated lysine. Furthermore, while many PWWP domains contain a β-barrel, there are significant differences in other structural aspects among PWWP domains<ref name="Hong">PMID:21720545</ref>. The aromatic cage in the β-barrel is a conserved structure among PWWP domains and is necessary for methyllysine binding<ref name="Hong" />. | |||
== '''Links to Human Disease''' == | == '''Links to Human Disease''' == | ||
BRPF1 has been implicated in the progression of several cancers. Chromosomal translocations of the gene encoding MOZ (a subunit in the MOZ HAT complex) have been linked to the development of acute myeloid leukemia <ref name="Obi" />. The crucial role of BRPF1 in this complex has made it the subject of many studies in order to understand how this mutation leads to | BRPF1 has been implicated in the progression of several cancers. Chromosomal translocations of the gene encoding MOZ (a subunit in the MOZ HAT complex) have been linked to the development of acute myeloid leukemia <ref name="Obi" />. The crucial role of BRPF1 in this complex has made it the subject of many studies in order to understand how this mutation leads to cancer. Another study reported an association between upregulation of the BRPF1 gene and poor survival rates in hepatocellular carcinoma patients <ref>PMID:34285329</ref>. | ||
Mutations within the gene itself have been associated with neurological disorders and widespread reduced histone acetylation <ref name="Yan" />. | Mutations within the gene itself have been associated with neurological disorders and widespread reduced histone acetylation <ref name="Yan" />. | ||
