How do eucaryotic gene activator proteins increase the rate of transcription initiation? 1.By activating directly on the transcription machinery. 2.By changing the chromatin structure.  Chromatin Remodeling

Epigenetics Any potentially stable and heritable change i n gene expression that occurs without a ch ange in DNA sequence

What does “epigenetics” mean? Literally, epigenetics means above, or on top of, genetics. Usually this means information coded beyond the DNA sequence, such as in covalent modifications to the DNA or modifications to the chromatin structure. Transcription Epigenetic Silencing

What does “epigenetics” mean? Practically, epigenetics describes phenomena in which genetically identical cells or organisms express their genomes differently, causing phenotypic differences. Genetically identical cells or individuals Different epigenetic modifications leading to different expression patterns

Epigenetic programming in plants helps control developmental transitions Embryonic development Vegetative development Reproductive development Vegetative to reproductive transition Embryonic to vegetative transition

XX X chromosome inactivation involves epigenetic silencing X X X X XX XX XX XX XX XX XX XX XX XX XX XX In female mammals, one copy of the X chromosome in each cell is epigenetically inactivated. Fur color in cats is determined in part by oran ge, an X-linked gene. A female cat that is hete rozygous for the orange gene shows black an d orange patches, corresponding to which X c hromosome is active. XX

Epigenetic marks and their maintenance DNA methylation Histone modifications Epigenetic genome regulation in plants Transposon silencing Control of flowering time Control of imprinted genes Gene silencing in trans; paramutation Resetting the epigenome

Chromosomes consist of heterochromatin and euchromatin Densely packaged heterochromatin Less densely packaged euchromatin DNA around the centrome re is usually packaged as heterochromatin. CENTROMERE

Heterochromatin and euchromatin form distinct domains in nuclei Euchromatin DAPI DNA stain Merged Centromeric heterochromatin

The Methylation of DNA Can Alter Patterns of Gene Expression ~ 70% of the 5’CpG-3’ sequence in mammalian genomes are methylated Inactive gene; hypermethylation Active gene; hypomethylation The methyl group of 5-methylcytosine protrudes into the major groove where it could easily interfere with the binding of proteins that stimulate transcription. Deamination of 5-methylcytosine results in thymine Most genes are found in CpG islands, regions of the genome that contain ~4 times as many CpG sequences as does the remainder of the genome.

DNA methylation O N NH 2 N ~ O N N ~ CH3 cytosine5-methylcytosine Methyltransferase DNA can be covalently modified by cytosine methylation. TTCGCCGACTAA Methyl-cy tosine

CG methylation can be propagated during DNA replication MET1 5’ A T G C G T A C T A T G C G T A C T T A C G C A T G A REPLICATION “MAINTENANCE” METHYLATION A T G C G T A C T T A C G C A T G A A T G C G T A C T T A C G C A T G A 3’ T A C G C A T G A A T G C G T A C T T A C G C A T G A

Heterochromatin DNA is highly methylated Although CG methylation is more abundant in pericentro meric regions, a higher prop ortion of CHH methylation is found there. BLUE = Gene density RED = Repetitive element density